2023
Long term structural and functional neural changes following a single infusion of Ketamine in PTSD
Duek O, Korem N, Li Y, Kelmendi B, Amen S, Gordon C, Milne M, Krystal J, Levy I, Harpaz-Rotem I. Long term structural and functional neural changes following a single infusion of Ketamine in PTSD. Neuropsychopharmacology 2023, 48: 1648-1658. PMID: 37270621, PMCID: PMC10517133, DOI: 10.1038/s41386-023-01606-3.Peer-Reviewed Original ResearchConceptsKetamine recipientsSingle infusionMain study outcomeTiming of administrationEnd of treatmentNMDA receptor antagonistFunctional neural changesFrequency of administrationSignificant clinical implicationsTrauma-focused psychotherapyBrief exposure therapyAmygdala-vmPFC connectivityPost-retrieval extinctionKetamine doseKetamine administrationReceptor antagonistTrauma scriptsNeural changesClinical implicationsDecreased connectivityExposure therapyKetamineTrauma memoriesStudy outcomesUncinate fasciculus
2019
A 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 ResearchConceptsDorsolateral 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 study2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE
Krystal J. 2. MICROCIRCUITS, MACROCIRCUITS, AND CORTICOL DYSFUNCTION IN SCHIZOPHRENIA: A COMPUTATIONAL AND TRANSLATIONAL NEUROSCIENCE PERSPECTIVE. Schizophrenia Bulletin 2018, 44: s1-s1. PMCID: PMC5887654, DOI: 10.1093/schbul/sby014.001.Peer-Reviewed Original ResearchNMDA glutamate receptorsNMDA receptor antagonistCortical functional connectivityPathophysiology of schizophreniaReceptor antagonistTranslational neuroscience perspectiveGlutamate receptorsHealthy humansAnimal modelsSchizophrenia patientsMemory impairmentNeuropsychiatric disordersSynaptic signalingFunctional connectivityNovel therapeuticsSchizophreniaDisordersPresentationPatientsPathophysiologyDysfunctionKetamineAntagonistSymptomsAbnormalities
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 groupsKetamine-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 decrease
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 ResearchConceptsMajor 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 efficacy
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
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 analysisIn 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
2013
Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans
Driesen NR, McCarthy G, Bhagwagar Z, Bloch M, Calhoun V, D'Souza DC, Gueorguieva R, He G, Ramachandran R, Suckow RF, Anticevic A, Morgan PT, Krystal JH. Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans. Molecular Psychiatry 2013, 18: 1199-1204. PMID: 23337947, PMCID: PMC3646075, DOI: 10.1038/mp.2012.194.Peer-Reviewed Original ResearchConceptsFunctional connectivityNegative symptomsGamma-aminobutyric acid (GABA) neuronsNMDA receptor antagonist ketamineAspartate glutamate receptor antagonistContinuous ketamine infusionGlutamate receptor antagonistsNMDA-R antagonistsCortical functional connectivityNMDA-R antagonist ketamineSchizophrenia-like symptomsHealthy human subjectsNegative Syndrome ScaleBrain functional connectivityPrimary samplesRegion-specific mannerFunctional magnetic resonanceKetamine infusionReceptor antagonistPathological increaseSyndrome ScaleSymptomsPreclinical researchKetamineBrain oscillationsConnectivity, Pharmacology, and Computation: Toward a Mechanistic Understanding of Neural System Dysfunction in Schizophrenia
Anticevic A, Cole MW, Repovs G, Savic A, Driesen NR, Yang G, Cho YT, Murray JD, Glahn DC, Wang XJ, Krystal JH. Connectivity, Pharmacology, and Computation: Toward a Mechanistic Understanding of Neural System Dysfunction in Schizophrenia. Frontiers In Psychiatry 2013, 4: 169. PMID: 24399974, PMCID: PMC3871997, DOI: 10.3389/fpsyt.2013.00169.Peer-Reviewed Original ResearchNMDA receptor antagonistFunctional neuroimaging toolsFunctional imaging studiesNeural system dysfunctionsRecent neuroimaging studiesKetamine administrationRecent findingsPharmacological treatmentSynaptic dysfunctionReceptor antagonistSystem dysfunctionPathophysiologic hypothesesBipolar illnessHealthy subjectsResting-state neuroimagingHealthy volunteersClinical investigationHealthy humansPsychiatric disordersCardinal featuresPharmacological manipulationPsychiatric conditionsLocal circuitsImaging studiesNeuropsychiatric diseases
2012
NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia
Anticevic A, Gancsos M, Murray JD, Repovs G, Driesen NR, Ennis DJ, Niciu MJ, Morgan PT, Surti TS, Bloch MH, Ramani R, Smith MA, Wang XJ, Krystal JH, Corlett PR. NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16720-16725. PMID: 23012427, PMCID: PMC3478611, DOI: 10.1073/pnas.1208494109.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlgorithmsBrainCognitionDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleHumansInfusions, IntravenousKetamineMagnetic Resonance ImagingMaleMemoryModels, NeurologicalPattern Recognition, VisualPsychomotor PerformanceReceptors, N-Methyl-D-AspartateSchizophreniaSynaptic TransmissionYoung AdultConceptsNeural systemsLarge-scale brain systemsTask-dependent activationN-methyl-D-aspartate receptorsRealistic computational modelingSevere neuropsychiatric illnessNMDA glutamate receptor antagonistGlutamate receptor antagonistsBrain systemsNMDA receptor functionTask performanceMultiple interacting regionsCognitionCortical disinhibitionGlutamatergic neurotransmissionReceptor antagonistCortical computationGlutamate's roleReciprocal relationshipNeuropsychiatric illnessLocal circuitsReceptor functionSchizophreniaPresent findingsComputational modelingCapturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans
Moghaddam B, Krystal JH. Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans. Schizophrenia Bulletin 2012, 38: 942-949. PMID: 22899397, PMCID: PMC3446228, DOI: 10.1093/schbul/sbs075.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsAntipsychotic AgentsBrief Psychiatric Rating ScaleCerebral CortexDisease Models, AnimalDopamineEmotionsGlutamic AcidHumansKetamineNeurosciencesPhencyclidinePsychoses, Substance-InducedReceptor, Metabotropic Glutamate 5Receptors, Dopamine D2Receptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateSchizophreniaSynapsesTranslational Research, BiomedicalConceptsNMDA receptor antagonistReceptor antagonistDopamine hypothesisN-methyl-D-aspartate receptor antagonistGlutamate synaptic functionTranslational neuroscience studiesTreatment of schizophreniaPathophysiology of schizophreniaPotential treatment targetPotential new targetsDopamine antagonistsCortical functionAnimal studiesTreatment targetsClinical testingSynaptic functionAntagonistTranslational toolSchizophreniaTranslational research fundingTranslational researchPotential mechanismsNew targetsAngel dustSystems neuroscienceMemantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activity in individuals with and without a family history of alcoholism
Jamadar S, DeVito EE, Jiantonio RE, Meda SA, Stevens MC, Potenza MN, Krystal JH, Pearlson GD. Memantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activity in individuals with and without a family history of alcoholism. Psychopharmacology 2012, 222: 129-140. PMID: 22311382, PMCID: PMC3674025, DOI: 10.1007/s00213-011-2628-2.Peer-Reviewed Original ResearchConceptsNMDA receptor antagonistFamily historyFHN subjectsReceptor antagonistFHP subjectsN-methyl-D-aspartate receptor functionReceptor functionIdentical-appearing placeboEffects of memantineFMRI activityNMDA receptor functionCorrect rejectsSingle doseMemantineGo/No-Go taskSeparate daysTemporal regionsCingulate activation
2011
Glutamatergic Modulation of Auditory Information Processing in the Human Brain
Gunduz-Bruce H, Reinhart RM, Roach BJ, Gueorguieva R, Oliver S, D'Souza DC, Ford JM, Krystal JH, Mathalon DH. Glutamatergic Modulation of Auditory Information Processing in the Human Brain. Biological Psychiatry 2011, 71: 969-977. PMID: 22036036, PMCID: PMC3290754, DOI: 10.1016/j.biopsych.2011.09.031.Peer-Reviewed Original ResearchConceptsN-acetylcysteineAuditory mismatch negativityReceptor antagonistN-methyl-D-aspartate receptor antagonistAspartate glutamate receptor antagonistOral N-acetylcysteinePlacebo-controlled studyGlutamate receptor antagonistsEffects of ketamineInfusion of salineMismatch negativityTest dayMMN amplitudeCystine-glutamate exchangerAuditory information processingP300 event-related potentialGlutamatergic modulationCognitive enhancing agentsEvent-related potentialsKetamine effectsHealthy volunteersHealthy humansSchizophrenia patientsPositive symptomsKetamine
2010
Characterization of the Interactive Effects of Glycine and D-Cycloserine in Men: Further Evidence for Enhanced NMDA Receptor Function Associated with Human Alcohol Dependence
Krystal JH, Petrakis IL, Limoncelli D, Nappi SK, Trevisan L, Pittman B, D'Souza DC. Characterization of the Interactive Effects of Glycine and D-Cycloserine in Men: Further Evidence for Enhanced NMDA Receptor Function Associated with Human Alcohol Dependence. Neuropsychopharmacology 2010, 36: 701-710. PMID: 21124304, PMCID: PMC3055693, DOI: 10.1038/npp.2010.203.Peer-Reviewed Original ResearchConceptsNMDA receptor functionAlcohol-dependent patientsHuman alcohol dependenceAntagonist-like effectsReceptor functionReceptor antagonistDCS effectsD-cycloserineAlcohol-like effectsAlcohol dependenceNMDA glutamate receptor functionN-methyl-D-aspartate (NMDA) glutamate receptor antagonistStandard alcohol drinksGlutamate receptor antagonistsChronic alcohol consumptionDouble-blind conditionsNMDA receptor antagonistAlcohol-dependent menGlutamate receptor functionAlcohol-dependent animalsPlasma levelsGlycine administrationGlycine levelsNMDA receptorsCoagonist siteThe interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects
Hallak JE, Dursun SM, Bosi DC, de Macedo LR, Machado-de-Sousa JP, Abrão J, Crippa JA, McGuire P, Krystal JH, Baker GB, Zuardi AW. The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2010, 35: 198-202. PMID: 21062637, DOI: 10.1016/j.pnpbp.2010.11.002.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleHealthy human subjectsGlutamate receptor systemMale healthy volunteersNMDA receptor antagonistEffects of ketamineTreatment of schizophreniaPsychiatric Rating ScaleHuman subjectsWeak partial agonistNon-significant trendKetamine administrationReceptor antagonistEndocannabinoid systemHealthy volunteersPartial agonistActivation subscalePsychiatric conditionsKetamineRandomized orderReceptor systemBehavioral effectsRating ScaleCannabidiolPreliminary evidence
2008
Ethanol-like effects of thiopental and ketamine in healthy humans
Dickerson D, Pittman B, Ralevski E, Perrino A, Limoncelli D, Edgecombe J, Acampora G, Krystal J, Petrakis I. Ethanol-like effects of thiopental and ketamine in healthy humans. Journal Of Psychopharmacology 2008, 24: 203-211. PMID: 19028835, PMCID: PMC4484757, DOI: 10.1177/0269881108098612.Peer-Reviewed Original ResearchConceptsEthanol-like effectsEthanol-related effectsNMDA receptor antagonistBlock NMDA receptorsNMDA receptor antagonismSeparate test daysGamma-aminobutyric acidReceptor antagonismSubanesthetic dosesReceptor antagonistNMDA receptorsFamily historyEthanol intoxicationHealthy humansPharmacological agentsEthanol effectsKetamineReceptor activityReceptor functionLarger studyBehavioral effectsThiopentalIntoxicationSubjective intoxicationTest day
2007
Effect of Memantine on Cue-Induced Alcohol Craving in Recovering Alcohol-Dependent Patients
Krupitsky EM, Neznanova O, Masalov D, Burakov AM, Didenko T, Romanova T, Tsoy M, Bespalov A, Slavina TY, Grinenko AA, Petrakis IL, Pittman B, Gueorguieva R, Zvartau EE, Krystal JH. Effect of Memantine on Cue-Induced Alcohol Craving in Recovering Alcohol-Dependent Patients. American Journal Of Psychiatry 2007, 164: 519-523. PMID: 17329479, DOI: 10.1176/ajp.2007.164.3.519.Peer-Reviewed Original ResearchConceptsNMDA receptor antagonist memantineAlcohol cue-induced cravingEffects of memantineAspartic acid (NMDA) glutamate receptorsDose-related fashionDouble-blind conditionsNMDA receptor functionNMDA receptor antagonistAlcohol-dependent patientsAlcohol cuesCue-induced alcoholTreatment of alcoholismCue-induced cravingEthanol-like effectsReceptor antagonistAlcohol-dependent inpatientsGlutamate receptorsMemantineAlcohol cravingMotivational disturbancesRandomized orderReceptor functionBehavioral effectsSubjective effectsTest day