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
2014
Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal
Cosgrove KP, McKay R, Esterlis I, Kloczynski T, Perkins E, Bois F, Pittman B, Lancaster J, Glahn DC, O’Malley S, Carson RE, Krystal JH. Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 18031-18036. PMID: 25453062, PMCID: PMC4273348, DOI: 10.1073/pnas.1413947111.Peer-Reviewed Original ResearchConceptsGABAA receptor levelsAlcohol withdrawalTobacco smokingReceptor levelsGABAA receptorsAlcohol-dependent smokersGABAA receptor availabilityMo of abstinenceProlonged alcohol withdrawalGABAA receptor systemCombination of alcoholNicotine blocksComorbid alcoholSustained elevationAlcohol abstinenceNicotine dependenceRobust elevationReceptor availabilityNicotine consumptionSmokingReceptor systemFirst weekNonhuman primatesControl levelsWithdrawal
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 ResearchMeSH KeywordsAlcoholismAnimalsDrug-Seeking BehaviorGlutamic AcidHumansMolecular Targeted TherapyProtein SubunitsReceptors, AMPAReceptors, Kainic AcidReceptors, N-Methyl-D-AspartateSubstance Withdrawal SyndromeConceptsGlutamate 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
The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Substance Use and Related Disorders. Part 2: Opioid dependence
Soyka M, Kranzler HR, van den Brink W, Krystal J, Möller HJ, Kasper S, Treatment G. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Substance Use and Related Disorders. Part 2: Opioid dependence. The World Journal Of Biological Psychiatry 2011, 12: 160-187. PMID: 21486104, DOI: 10.3109/15622975.2011.561872.Peer-Reviewed Original ResearchMeSH KeywordsAdultAryl Hydrocarbon HydroxylasesBuprenorphineCytochrome P-450 CYP2B6Cytochrome P-450 CYP2D6Drug Therapy, CombinationEvidence-Based MedicineGenetic VariationHumansMethadoneNarcotic AntagonistsNarcoticsOpiate Substitution TreatmentOpioid-Related DisordersOxidoreductases, N-DemethylatingPsychotherapyReceptors, OpioidSocial SupportStandard of CareSubstance Withdrawal SyndromeConceptsOpioid dependenceOpioid abusePractice guidelinesEvidence-based practice guidelinesBiological Psychiatry (WFSBP) GuidelinesOpioid agonist methadoneSecond-line medicationsNational treatment guidelinesNumber of medicationsEfficacy of methadoneOpioid use disorderEvidence-based guidelinesRandomized clinical trialsCombination of buprenorphineWorld FederationInternational task forceStrength of evidenceOpioid withdrawalAdjunctive medicationsOpioid maintenanceTreatment guidelinesTask ForceCochrane LibraryPharmacological treatmentClinical trials
2009
Dopamine and Serotonin Transporter Availability During Acute Alcohol Withdrawal: Effects of Comorbid Tobacco Smoking
Cosgrove KP, Krantzler E, Frohlich EB, Stiklus S, Pittman B, Tamagnan GD, Baldwin RM, Bois F, Seibyl JP, Krystal JH, O'Malley SS, Staley JK. Dopamine and Serotonin Transporter Availability During Acute Alcohol Withdrawal: Effects of Comorbid Tobacco Smoking. Neuropsychopharmacology 2009, 34: 2218-2226. PMID: 19440191, PMCID: PMC4457331, DOI: 10.1038/npp.2009.49.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol DrinkingBrainBrain MappingCase-Control StudiesCocaineDopamine Plasma Membrane Transport ProteinsFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedProtein BindingRadiopharmaceuticalsSerotonin Plasma Membrane Transport ProteinsSmokingStatistics as TopicSubstance Withdrawal SyndromeTomography, Emission-Computed, Single-PhotonYoung AdultConceptsDA transporter availabilityTobacco smokingSerotonin transporter availabilityTransporter availabilityAlcohol drinkersAcute withdrawalAlcohol drinkingLast drinkCIT single photon emissionAcute alcohol withdrawalHeavy alcohol drinkingSingle photon emissionEffects of alcoholControl smokersAlcohol withdrawalSynaptic markersNeuroadaptive changesNonsmokersSmokersSmokingTotal groupBrainstemSignificant positive correlationFirst weekPrevious month
2007
Multidimensionality of the Alcohol Withdrawal Symptom Checklist: A Factor Analysis of the Alcohol Withdrawal Symptom Checklist and CIWA‐Ar
Pittman B, Gueorguieva R, Krupitsky E, Rudenko AA, Flannery BA, Krystal JH. Multidimensionality of the Alcohol Withdrawal Symptom Checklist: A Factor Analysis of the Alcohol Withdrawal Symptom Checklist and CIWA‐Ar. Alcohol Clinical And Experimental Research 2007, 31: 612-618. PMID: 17374040, DOI: 10.1111/j.1530-0277.2007.00345.x.Peer-Reviewed Original ResearchConceptsAlcohol withdrawal syndromeCIWA-ArClinical Institute Withdrawal Assessment-AlcoholSymptom ChecklistCIWA-Ar scoresFirst study dayInpatient treatment unitAlcohol-dependent male inpatientsObserver-rated scalesAlcohol withdrawalWithdrawal syndromeTension/anxietyMale inpatientsIndependent factorsStudy daysClinical relevanceSelf-rating scaleAlcohol cravingObserver-rated measuresDiscriminative valueSelf-rated measuresInitial weeksAutonomic arousalFace validityResearch settingsAntiglutamatergic Strategies for Ethanol Detoxification: Comparison With Placebo and Diazepam
Krupitsky EM, Rudenko AA, Burakov AM, Slavina TY, Grinenko AA, Pittman B, Gueorguieva R, Petrakis IL, Zvartau EE, Krystal JH. Antiglutamatergic Strategies for Ethanol Detoxification: Comparison With Placebo and Diazepam. Alcohol Clinical And Experimental Research 2007, 31: 604-611. PMID: 17374039, DOI: 10.1111/j.1530-0277.2007.00344.x.Peer-Reviewed Original ResearchConceptsAlcohol withdrawal symptomsWithdrawal symptomsActive medicationAlcohol withdrawalGlutamatergic activationEthanol detoxificationAspartate glutamate receptor antagonistGlutamate release inhibitorGlutamate receptor antagonistsMale alcohol-dependent inpatientsAdditional diazepamDiazepam administrationClinical evidenceStandard pharmacotherapyReceptor antagonistAlcohol-dependent inpatientsRelease inhibitorEthanol dependenceAlcohol abstinenceGlutamate receptorsReceptor inhibitorsWithdrawal severityPlaceboMedicationsNew treatments
2006
γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment
Krystal JH, Staley J, Mason G, Petrakis IL, Kaufman J, Harris RA, Gelernter J, Lappalainen J. γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment. JAMA Psychiatry 2006, 63: 957-968. PMID: 16952998, DOI: 10.1001/archpsyc.63.9.957.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismBenzodiazepinesBrainCerebral CortexGamma-Aminobutyric AcidGene ExpressionGenetic Predisposition to DiseaseHumansReceptors, GABA-ARisk FactorsSubstance Withdrawal SyndromeConceptsBrain GABA systemsGABA systemAlcohol dependenceWithdrawal symptomsGABA functionGamma-aminobutyric acid (GABA) functionCortical GABA levelsAlcohol withdrawal symptomsΓ-Aminobutyric Acid Type A ReceptorsEnvironmental risk factorsLong-term alcohol effectsType A ReceptorsAlcohol-dependent individualsLong-term sobrietyGABA releaseNeurosteroid levelsAcute withdrawalAlcoholism vulnerabilityGABA neurotransmissionRisk factorsGABA levelsExtrasynaptic locationsLow chloride conductanceReceptor densityTonic component
2005
Cortical γ-Aminobutyric Acid Type A–Benzodiazepine Receptors in Recovery From Alcohol Dependence: Relationship to Features of Alcohol Dependence and Cigarette Smoking
Staley JK, Gottschalk C, Petrakis IL, Gueorguieva R, O’Malley S, Baldwin R, Jatlow P, Verhoeff NP, Perry E, Weinzimmer D, Frohlich E, Ruff E, van Dyck CH, Seibyl JP, Innis RB, Krystal JH. Cortical γ-Aminobutyric Acid Type A–Benzodiazepine Receptors in Recovery From Alcohol Dependence: Relationship to Features of Alcohol Dependence and Cigarette Smoking. JAMA Psychiatry 2005, 62: 877-888. PMID: 16061765, DOI: 10.1001/archpsyc.62.8.877.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcoholismCerebral CortexComorbidityEthanolFlumazenilHumansIodine RadioisotopesMaleReceptors, GABA-ASmokingSubstance Withdrawal SyndromeTemperanceTomography, Emission-Computed, Single-PhotonConceptsWeeks of abstinenceIomazenil single-photon emissionSingle photon emissionDays of sobrietyAlcohol dependenceIomazenil uptakeTomographic scanBenzodiazepine receptorsVoxel-based statistical parametric mappingReceptor adaptationDistribution volumeReceptor functionGamma-aminobutyric acid type ABenzodiazepine receptor levelsIodine I 123Reduced receptor functionHuman alcohol dependenceLast alcoholic drinkHealthy comparison groupStatistical parametric mappingAlcohol withdrawalClinical featuresSmoking statusCigarette smokingAcute withdrawal
2003
Neurobiological Correlates of the Disposition and Maintenance of Alcoholism
Heinz A, Schäfer M, Higley J, Krystal J, Goldman D. Neurobiological Correlates of the Disposition and Maintenance of Alcoholism. Pharmacopsychiatry 2003, 36: 255-258. PMID: 14677088, DOI: 10.1055/s-2003-45139.Peer-Reviewed Original ResearchConceptsAlcohol effectsMaintenance of alcoholismCurrent disease conceptsNeurobiological foundationsDispositional factorsNeurobiological correlatesMotivational therapyConsequences of alcoholismAlcohol cravingReward systemAlcohol intakeClinical withdrawalReduced controlTreatment of alcoholismChronic alcohol effectsNew treatment optionsNeuroadaptationsResearch pointsRelapse riskMonoaminergic dysfunctionPatient groupTreatment optionsGlutamatergic neurotransmissionCentral GABAergicPharmacological approachesN-methyl-d-aspartate glutamate receptors and alcoholism: reward, dependence, treatment, and vulnerability
Krystal JH, Petrakis IL, Mason G, Trevisan L, D'Souza DC. N-methyl-d-aspartate glutamate receptors and alcoholism: reward, dependence, treatment, and vulnerability. Pharmacology & Therapeutics 2003, 99: 79-94. PMID: 12804700, DOI: 10.1016/s0163-7258(03)00054-8.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingAlcoholismAnimalsClinical Trials as TopicDisease SusceptibilityEthanolHumansReceptors, N-Methyl-D-AspartateRewardRisk FactorsSubstance Withdrawal SyndromeConceptsGlutamatergic systemEthanol abuseGlutamate receptorsN-methyl-D-aspartate (NMDA) subtypePrimary excitatory neurotransmitterAspartate glutamate receptorsAction of ethanolEthanol withdrawalGlutamatergic agentsGlutamatergic functionExcitatory neurotransmitterTranslational neuroscience perspectiveGlutamate systemEthanol intoxicationBehavioral effectsEthanol contributeAlcoholismBrainReceptorsTreatmentAbuseN-methylSubtypesNeurotransmittersIntoxication
2002
Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients
Stine SM, Southwick SM, Petrakis IL, Kosten TR, Charney DS, Krystal JH. Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients. Biological Psychiatry 2002, 51: 642-651. PMID: 11955464, DOI: 10.1016/s0006-3223(01)01292-6.Peer-Reviewed Original ResearchConceptsOpioid-dependent patientsBlood pressureMethadone patientsOpioid dependenceHPA axis perturbationsPlacebo-controlled studyDiastolic blood pressureSystolic blood pressureMethadone-maintained patientsSymptom scale scoresSynaptic noradrenalineOpioid withdrawalPostsynaptic effectsMHPG levelsAbstinence symptomsAdrenal axisOpioid drugsYohimbine effectNoradrenergic regulationHealthy volunteersHeart ratePhysiologic measuresPatientsCortisol levelsScale score
1999
CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls: Prediction of Alcohol Cue‐Induced Craving?
Petrakis I, Trevisan L, D'Souza C, Gil R, Krasnicki S, Webb E, Heninger G, Cooney N, Krystal J. CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls: Prediction of Alcohol Cue‐Induced Craving? Alcohol Clinical And Experimental Research 1999, 23: 1336-1341. PMID: 10470976, DOI: 10.1111/j.1530-0277.1999.tb04355.x.Peer-Reviewed Original ResearchConceptsAlcohol-dependent patientsHealthy controlsEndorphin levelsCSF levelsMonoamine metabolitesCSF measuresHealthy subjectsNorepinephrine metabolite MHPGLower CSF levelsBeta-endorphin levelsEarly-onset patientsCerebrospinal fluid levelsLate-onset patientsCentral neurotransmitter systemsCSF monoamine metabolitesDopamine metabolite HVAAlcohol cue exposureAlcohol-dependent individualsCue-Induced CravingAlcohol cue reactivityLumbar punctureMetabolite HVANeurotransmitter systemsMonoaminergic dysregulationMetabolite MHPG
1998
Complications of alcohol withdrawal: pathophysiological insights.
Trevisan LA, Boutros N, Petrakis IL, Krystal JH. Complications of alcohol withdrawal: pathophysiological insights. Alcohol Research 1998, 22: 61-6. PMID: 15706735, PMCID: PMC6761825.Peer-Reviewed Original ResearchConceptsAcute alcohol withdrawalAlcohol withdrawalLong-term sobrietyDelirium tremensAcute withdrawalMental confusionSignificant illnessPathophysiological insightsDisease processPsychiatric problemsCognitive impairmentComplicationsHeavy drinkingMemory disordersWithdrawalDeliriumMedicationsRelapseTremensPatientsSeizuresIllnessImpairmentSeverityHallucinations
1996
Nimodipine reduction of naltrexone-precipitated locus coeruleus activation and abstinence behavior in morphine-dependent rats
Krystal J, Compere S, Nestler E, Rasmussen K. Nimodipine reduction of naltrexone-precipitated locus coeruleus activation and abstinence behavior in morphine-dependent rats. Physiology & Behavior 1996, 59: 863-866. PMID: 8778878, DOI: 10.1016/0031-9384(95)02206-6.Peer-Reviewed Original ResearchConceptsL-type calcium channel antagonistLocus coeruleus neuronsMorphine-dependent ratsOpiate-dependent ratsCalcium channel antagonistsSingle-unit recordingsLocus coeruleus activationNimodipine effectCoeruleus neuronsNoradrenergic mechanismsOpiate withdrawalLocus coeruleusChannel antagonistsAnesthetized animalsNimodipineAbstinence behaviorTime courseRatsWithdrawal behaviorActivationNaltrexoneCoeruleus
1995
Mazindol treatment for cocaine dependence
Stine S, Krystal J, Kosten T, Charney D. Mazindol treatment for cocaine dependence. Drug And Alcohol Dependence 1995, 39: 245-252. PMID: 8556974, DOI: 10.1016/0376-8716(95)01174-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultCentral Nervous System StimulantsCocaineDouble-Blind MethodFemaleHumansMaleMazindolNeurologic ExaminationSubstance Abuse DetectionSubstance Withdrawal SyndromeSubstance-Related DisordersDiscontinuing Anticonvulsant Treatment of Aggression
HILLBRAND M, YOUNG J, KRYSTAL J. Discontinuing Anticonvulsant Treatment of Aggression. Journal Of Neuropsychiatry 1995, 7: 116-a-117. PMID: 7711482, DOI: 10.1176/jnp.7.1.116-a.Peer-Reviewed Original ResearchOpiate Dependence and Withdrawal: Preliminary Assessment Using Single Photon Emission Computerized Tomography (SPECT)
Krystal J, Woods S, Kosten T, Rosen M, Seibyl J, Van Dyck C, Price L, Zubal I, Hoffer P, Charney D. Opiate Dependence and Withdrawal: Preliminary Assessment Using Single Photon Emission Computerized Tomography (SPECT). The American Journal Of Drug And Alcohol Abuse 1995, 21: 47-63. PMID: 7762544, DOI: 10.3109/00952999509095229.Peer-Reviewed Original ResearchConceptsRegional brain functionOpiate withdrawal signsSingle Photon Emission Computerized TomographyHealthy subjectsNaloxone administrationOpiate withdrawalOpiate dependenceBrain functionParietal cortexHexamethylpropyleneamine oximeWithdrawal signsNaloxone effectChronic opiate dependencePlacebo-controlled studyRegional alterationsComparison of patientsMethadone-maintained patientsRegional cerebral perfusionPhoton Emission Computerized TomographyOpiate-dependent patientsRight temporal cortexRight parietal cortexFunctional brain imaging technologiesSingle photon emissionEmission computerized tomography
1994
SPECT regional cerebral blood flow alterations in naltrexone-precipitated withdrawal from buprenorphine
van Dyck C, Rosen M, Thomas H, McMahon T, Wallace E, O'Connor P, Sullivan M, Krystal J, Hoffer P, Woods S, Kosten T. SPECT regional cerebral blood flow alterations in naltrexone-precipitated withdrawal from buprenorphine. Psychiatry Research 1994, 55: 181-191. PMID: 7701033, DOI: 10.1016/0925-4927(94)90013-2.Peer-Reviewed Original ResearchConceptsRegional cerebral blood flowRegional cerebral blood flow alterationsCerebral blood flow alterationsHexamethyl propylene amine oximeOpiate-induced analgesiaBlood flow alterationsSeverity of withdrawalCerebral blood flowOpiate-dependent patientsAnterior cingulate regionsAnterior cingulate cortexSingle photon emissionPlacebo administrationAmine oximeOpiate withdrawalRCBF ratiosWithdrawal severityBlood flowCingulate cortexCingulate regionsSignificant negative correlationBuprenorphineNaltrexonePlaceboPatients
1992
Baclofen-assisted detoxification from opiates A pilot study
Krystal J, McDougle C, Kosten T, Price L, Aghajanian G, Charney D. Baclofen-assisted detoxification from opiates A pilot study. Journal Of Substance Use And Addiction Treatment 1992, 9: 139-142. PMID: 1324986, DOI: 10.1016/0740-5472(92)90081-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBaclofenFemaleHumansMaleMethadoneNeurologic ExaminationOpioid-Related DisordersSubstance Abuse Treatment CentersSubstance Withdrawal SyndromeConceptsOpen-label pilot studyPilot studyLabel pilot studyOpiate-dependent patientsAbrupt discontinuationOral dosesOpiate detoxificationAdjunctive rolePrimary treatmentOpiate dependencePatientsBaclofenInsufficient suppressionDose rangeMyalgiaVomitingClonidineDiscontinuationMedicationsHeadacheMethadoneDetoxificationDoses