2020
Continuous Ketamine Infusion for Pain as an Opportunity for Psychotherapy for PTSD: A Case Series of Ketamine-Enhanced Psychotherapy for PTSD and Pain (KEP-P2)
Keizer BM, Roache JD, Jones JR, Kalpinski RJ, Porcerelli JH, Krystal JH. Continuous Ketamine Infusion for Pain as an Opportunity for Psychotherapy for PTSD: A Case Series of Ketamine-Enhanced Psychotherapy for PTSD and Pain (KEP-P2). Psychotherapy And Psychosomatics 2020, 89: 326-329. PMID: 32248200, DOI: 10.1159/000507095.Peer-Reviewed Original Research
2019
Influence of combined treatment with naltrexone and memantine on alcohol drinking behaviors: a phase II randomized crossover trial
Krishnan-Sarin S, O’Malley S, Franco N, Cavallo DA, Tetrault JM, Shi J, Gueorguieva R, Pittman B, Krystal JH. Influence of combined treatment with naltrexone and memantine on alcohol drinking behaviors: a phase II randomized crossover trial. Neuropsychopharmacology 2019, 45: 319-326. PMID: 31590179, PMCID: PMC6901445, DOI: 10.1038/s41386-019-0536-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol DrinkingCross-Over StudiesDouble-Blind MethodDrug SynergismDrug Therapy, CombinationExcitatory Amino Acid AntagonistsFemaleHumansMaleMemantineNaltrexoneNarcotic AntagonistsYoung AdultConceptsAlcohol drinking behaviorFirst treatment periodTreatment periodNumber of drinksCrossover trialDrinking behaviorEfficacy of naltrexoneOpioid antagonist naltrexoneNMDA antagonist memantinePositive family historyDay treatment periodSelf-administration periodAlcohol-induced stimulationAd lib accessMemantine treatmentAntagonist naltrexoneOpioid systemFamily historyNTXPriming drinkMemantineNaltrexoneAlcohol cravingHeavy drinkersAlcohol dependenceRepeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial
Abdallah CG, Roache JD, Averill LA, Young-McCaughan S, Martini B, Gueorguieva R, Amoroso T, Southwick SM, Guthmiller K, López-Roca AL, Lautenschlager K, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH, PTSD F. Repeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial. Contemporary Clinical Trials 2019, 81: 11-18. PMID: 30999057, DOI: 10.1016/j.cct.2019.04.009.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStudy drugClinical trialsTherapeutic effectPharmacotherapy of PTSDFirst placebo-controlled trialPlacebo-controlled clinical trialActive duty military populationDose-related efficacyMedication treatment optionsPlacebo-controlled trialDose-related effectsNovel neural mechanismActive duty militaryKetamine infusionSerotonergic antidepressantsEligible participantsTreatment optionsCase reportNew drug developmentOnly trialSustained reductionVeteran populationDrug AdministrationPilot evidenceKetamine: A Paradigm Shift for Depression Research and Treatment
Krystal JH, Abdallah CG, Sanacora G, Charney DS, Duman RS. Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron 2019, 101: 774-778. PMID: 30844397, PMCID: PMC6560624, DOI: 10.1016/j.neuron.2019.02.005.Peer-Reviewed Original ResearchA multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms
Fleming LM, Javitt DC, Carter CS, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman J, Krystal JH, Corlett PR. A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms. NeuroImage Clinical 2019, 22: 101739. PMID: 30852397, PMCID: PMC6411494, DOI: 10.1016/j.nicl.2019.101739.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultBrainExcitatory Amino Acid AntagonistsFemaleHumansKetamineMagnetic Resonance ImagingMaleMiddle AgedNerve NetSchizophreniaYoung AdultConceptsDorsolateral prefrontal cortexN-methyl-D-aspartate (NMDA) glutamate receptor antagonistFunctional connectivityKetamine-induced alterationsGlutamate receptor antagonistsAltered brain functionState functional connectivityRsfMRI connectivityRisk patientsMulticenter studyKetamine effectsReceptor antagonistDLPFC connectivityMimic symptomsHealthy individualsKetamine usePositive symptomsCertain biomarkersBrain functionPrefrontal cortexPatientsConnectivity signaturesSeed-based measuresSchizophreniaKetamine
2018
The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects
Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GMI, Purohit P, de Graaf RA, Esterlis I, Juchem C, Pittman BP, Krystal JH, Rothman DL, Sanacora G, Mason GF. The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology 2018, 43: 2154-2160. PMID: 29977074, PMCID: PMC6098048, DOI: 10.1038/s41386-018-0136-3.Peer-Reviewed Original ResearchConceptsGlutamate-glutamine cyclingGlutamate neurotransmissionAntidepressant effectsKetamine effectsRodent studiesN-methyl-D-aspartate receptor antagonistRapid antidepressant effectsClinician-Administered Dissociative States ScaleEffects of ketamineGlutamine enrichmentKetamine infusionGlutamate releaseKetamine administrationSubanesthetic dosesPsychotomimetic effectsReceptor antagonistNormal salineSchizophrenia pathophysiologyFrontal cortexMRS scansDepressed subjectsKetamineNeurotransmissionPrefrontal cortexPilot studySimilar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia
Cheng WJ, Chen CH, Chen CK, Huang MC, Pietrzak RH, Krystal JH, Xu K. Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia. Schizophrenia Research 2018, 199: 313-318. PMID: 29510925, DOI: 10.1016/j.schres.2018.02.049.Peer-Reviewed Original ResearchMeSH KeywordsAdultCognitionCognitive DysfunctionExcitatory Amino Acid AntagonistsFemaleHumansKetamineMalePsychotic DisordersSchizophrenic PsychologySubstance-Related DisordersConceptsSZ patientsCognitive impairmentCognitive functionSocial-emotional cognitionCogstate Brief BatteryPsychomotor processing speedTreatment-seeking patientsSpatial problemsSymptom profilesSevere symptom profileVerbal memoryCognitive profileKetamine-dependent patientsVisual learningBrief batteryProcessing speedNegative Syndrome ScaleBiology of psychosisKetamine usersCognitive dysfunctionPersistent psychosisMemorySubscale scoresKetamine abuseMinority of users
2017
Metabotropic Glutamatergic Receptor 5 and Stress Disorders: Knowledge Gained From Receptor Imaging Studies
Esterlis I, Holmes SE, Sharma P, Krystal JH, DeLorenzo C. Metabotropic Glutamatergic Receptor 5 and Stress Disorders: Knowledge Gained From Receptor Imaging Studies. Biological Psychiatry 2017, 84: 95-105. PMID: 29100629, PMCID: PMC5858955, DOI: 10.1016/j.biopsych.2017.08.025.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPositron emission tomography studyEmission tomography studiesMGluR5 modulationAntidepressant responseStress disorderBipolar disorderStress-related psychiatric disordersTomography studyAntagonism of mGluR5Ketamine’s antidepressant responseSignificant side effectsPromising therapeutic targetReceptor imaging studiesPosttraumatic stress disorderMDD heterogeneityManic mood statesAntidepressant efficacyObsessive-compulsive disorderDepressive disorderSubtype 5Neurotransmitter systemsPsychiatric disordersReceptor 5Side effectsSynaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic
Krystal JH, Abdallah CG, Averill LA, Kelmendi B, Harpaz-Rotem I, Sanacora G, Southwick SM, Duman RS. Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic. Current Psychiatry Reports 2017, 19: 74. PMID: 28844076, PMCID: PMC5904792, DOI: 10.1007/s11920-017-0829-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalExcitatory Amino Acid AntagonistsHumansKetamineNeurobiologyStress Disorders, Post-TraumaticSynaptic TransmissionConceptsSynaptic connectivityRapid-acting treatmentPathophysiology of PTSDPotential clinical importanceTreatment of PTSDSynaptic lossPurpose of ReviewStudiesDisconnection syndromeClinical importanceNovel pharmacotherapeuticsNovel therapeuticsPTSD symptomsRecent FindingsHerePTSDPathophysiologyKetamineTreatmentDisordersTherapeutic applicationsStress-related lossesSyndromeSymptomsPharmacotherapeuticsKetamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression
Esterlis I, DellaGioia N, Pietrzak RH, Matuskey D, Nabulsi N, Abdallah CG, Yang J, Pittenger C, Sanacora G, Krystal JH, Parsey RV, Carson RE, DeLorenzo C. Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression. Molecular Psychiatry 2017, 23: 824-832. PMID: 28397841, PMCID: PMC5636649, DOI: 10.1038/mp.2017.58.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMGluR5 availabilityPositron emission tomographyKetamine administrationControl groupAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced reductionMetabotropic glutamatergic receptorsRapid antidepressant effectsGlutamate receptor antagonistsKetamine-induced changesEffects of ketaminePET imaging studiesMechanism of actionGlutamate surgeAntidepressant effectsAntidepressant efficacyAntidepressant responseGlutamatergic receptorsControl subjectsReceptor antagonistHealthy controlsDepressive disorderSustained decreaseAlcohol Triggers Reemergence of Ketamine-Like Experience in a Ketamine Ex-User
Chang F, Xu K, Huang MC, Krystal JH. Alcohol Triggers Reemergence of Ketamine-Like Experience in a Ketamine Ex-User. Journal Of Clinical Psychopharmacology 2017, 37: 110-112. PMID: 28027112, PMCID: PMC5193231, DOI: 10.1097/jcp.0000000000000635.Peer-Reviewed Original ResearchAdultCentral Nervous System DepressantsEthanolExcitatory Amino Acid AntagonistsHumansKetamineMaleReceptors, N-Methyl-D-AspartateSubstance-Related Disorders
2016
KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS. Depression And Anxiety 2016, 33: 689-697. PMID: 27062302, PMCID: PMC4961540, DOI: 10.1002/da.22501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsDepressive Disorder, MajorExcitatory Amino Acid AntagonistsHumansKetamineReceptors, N-Methyl-D-AspartateConceptsMajor depressive disorderAntidepressant effectsKetamine's mechanismN-methyl-D-aspartate receptor antagonistRapid-acting antidepressant effectsPrefrontal cortexSingle subanesthetic doseRapid antidepressant effectsTreatment-resistant depressionFull therapeutic effectEfficacy of ketamineKetamine's antidepressant effectsRapid acting antidepressantsFuture clinical prospectsGlutamate surgeTraditional antidepressantsAntidepressant medicationCascade of eventsReceptor antagonistSubanesthetic doseDepressive disorderClinical dataTherapeutic effectTreatment responseLimited efficacySynaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman RS, Aghajanian GK, Sanacora G, Krystal JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nature Medicine 2016, 22: 238-249. PMID: 26937618, PMCID: PMC5405628, DOI: 10.1038/nm.4050.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsBrain-Derived Neurotrophic FactorCytokinesDepressive DisorderDiabetes MellitusExcitatory Amino Acid AntagonistsFemaleGlucocorticoidsHumansHypothalamo-Hypophyseal SystemInflammationKetamineMaleNeuronal PlasticityPituitary-Adrenal SystemSelective Serotonin Reuptake InhibitorsSex FactorsSignal TransductionStress, PsychologicalTime Factors
2015
Familial Alcoholism Risk and the Ratio of Stimulant to Sedative Effects of Ketamine
Yoon G, Pittman B, Limoncelli D, Krystal JH, Petrakis IL. Familial Alcoholism Risk and the Ratio of Stimulant to Sedative Effects of Ketamine. Biological Psychiatry 2015, 79: e69-e70. PMID: 26475672, DOI: 10.1016/j.biopsych.2015.09.006.Peer-Reviewed Original ResearchKetamine as a promising prototype for a new generation of rapid‐acting antidepressants
Abdallah CG, Averill LA, Krystal JH. Ketamine as a promising prototype for a new generation of rapid‐acting antidepressants. Annals Of The New York Academy Of Sciences 2015, 1344: 66-77. PMID: 25727103, PMCID: PMC4412785, DOI: 10.1111/nyas.12718.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive Agents, Second-GenerationBiomarkersDepressionExcitatory Amino Acid AntagonistsHumansKetamineWounds and InjuriesConceptsOpen-label studyRobust antidepressant effectsRapid-acting antidepressantsNeurobiology of depressionRoute of administrationModerate adverse effectsMechanism of actionTrauma-related disordersTraditional antidepressantsAntidepressant effectsTransient mildChronic treatmentControlled TrialsClinical effectsOptimal dosingPsychopharmacologic interventionsPatient groupPatient populationTreatment targetsKetamineAntidepressantsRelevant biomarkersAdverse effectsNeurobiological underpinningsInfusionN‐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 ResearchMeSH KeywordsAdultAlcohol DrinkingAlcohol-Related DisordersCravingCuesDose-Response Relationship, DrugExcitatory Amino Acid AntagonistsFemaleHumansImpulsive BehaviorMaleMemantineConceptsAlcohol 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
2014
Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia
Xu K, Krystal JH, Ning Y, Chen da C, He H, Wang D, Ke X, Zhang X, Ding Y, Liu Y, Gueorguieva R, Wang Z, Limoncelli D, Pietrzak RH, Petrakis IL, Zhang X, Fan N. Preliminary analysis of positive and negative syndrome scale in ketamine-associated psychosis in comparison with schizophrenia. Journal Of Psychiatric Research 2014, 61: 64-72. PMID: 25560772, PMCID: PMC4445679, DOI: 10.1016/j.jpsychires.2014.12.012.Peer-Reviewed Original ResearchConceptsKetamine groupNegative Syndrome ScaleSchizophrenia groupSyndrome ScaleN-methyl-D-aspartate (NMDA) glutamate receptor antagonistGlutamate receptor antagonistsPotential confounding factorsEarly course schizophreniaSymptom dimensionsSymptoms of schizophreniaReceptor antagonistChronic schizophreniaHealthy subjectsKetamine abuseSchizophrenia psychosisSchizophrenia patientsConfounding factorsSymptom severitySymptomsInpatientsSchizophreniaPsychosisKetamine usersDissociation symptomsPrincipal component factor analysisKetamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics
Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics. Annual Review Of Medicine 2014, 66: 1-15. PMID: 25341010, PMCID: PMC4428310, DOI: 10.1146/annurev-med-053013-062946.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsBrainDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantExcitatory Amino Acid AntagonistsGlutamic AcidHumansKetamineMood DisordersNeuronal PlasticityPrefrontal CortexConceptsRapid antidepressant effectsAntidepressant effectsGlutamate-based antidepressantsTolerability of ketamineRapid-acting antidepressantsTreatment-resistant depressionNeurobiology of depressionPotent antidepressant effectsRapid acting antidepressantsBiology of depressionPotential treatment targetHours of treatmentTreatment targetsKetamineAntidepressantsBiomarker studiesDepressionNeurobiologyTolerabilityN-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia
Anticevic A, Corlett PR, Cole MW, Savic A, Gancsos M, Tang Y, Repovs G, Murray JD, Driesen NR, Morgan PT, Xu K, Wang F, Krystal JH. N-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia. Biological Psychiatry 2014, 77: 569-580. PMID: 25281999, DOI: 10.1016/j.biopsych.2014.07.022.Peer-Reviewed Original ResearchMeSH KeywordsAdultChronic DiseaseExcitatory Amino Acid AntagonistsFemaleHumansKetamineMaleNeural PathwaysPrefrontal CortexSchizophreniaYoung AdultConceptsHealthy volunteersFunctional connectivityKetamine effectsChronic schizophreniaIllness progressionChronic illnessHigh riskRecent pharmacologic studiesReceptor antagonist effectsAspartate glutamate receptorsStages of schizophreniaCourse of schizophreniaGlutamate dysfunctionPharmacologic modelsPrefrontal cortex functionIllness stageNMDAR antagonistsFunctional dysconnectivityGlutamate receptorsPharmacologic studiesHealthy subjectsSchizophrenia onsetFunctional alterationsDevelopment of therapeuticsAntagonist effectsIn Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5
DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C, Yang J, Wen R, Mann JJ, Krystal JH, Parsey RV, Carson RE, Esterlis I. In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5. Biological Psychiatry 2014, 77: 266-275. PMID: 25156701, PMCID: PMC4277907, DOI: 10.1016/j.biopsych.2014.06.024.Peer-Reviewed Original ResearchConceptsSubtype 5Ketamine administrationPET scansMetabotropic glutamate receptor subtype 5Prefrontal cortexAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced effectsPositron emission tomography (PET) ligandGlutamate receptor antagonistsVolume of distributionMedial prefrontal cortexNegative allosteric modulatorsKetamine initiationGlutamate releaseDorsal putamenKetamine responseSubanesthetic dosesOrbital prefrontal cortexReceptor antagonistAcute effectsBolus injectionDorsal caudateArterial bloodScan 1