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 study
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
2012
Capturing 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 neuroscience
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
2000
Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects of N-methyl-D-aspartate Receptor Antagonists
Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH. Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine: Support for Hyperglutamatergic Effects of N-methyl-D-aspartate Receptor Antagonists. JAMA Psychiatry 2000, 57: 270-276. PMID: 10711913, DOI: 10.1001/archpsyc.57.3.270.Peer-Reviewed Original ResearchMeSH KeywordsAdultAffectBrief Psychiatric Rating ScaleCognition DisordersDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleGlutamatesHumansKetamineLamotrigineMaleMental DisordersPerceptual DisordersPlacebosPsychiatric Status Rating ScalesReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologyTriazinesVerbal LearningConceptsN-methyl-D-aspartate receptor antagonistNMDA receptor dysfunctionReceptor antagonistNeuropsychiatric effectsGlutamate releaseReceptor dysfunctionSymptom subscalesPlacebo 2 hoursClinician-Administered Dissociative States ScaleAdministration of lamotrigineAdministration of ketamineDouble-blind conditionsNMDA receptor antagonistMood-elevating effectsPositive symptom subscaleBrief Psychiatric RatingNovel therapeutic agentsNegative symptom subscaleHopkins Verbal Learning TestVerbal Learning TestKetamine effectsPsychiatric illnessHealthy subjectsPathophysiologic processesPreclinical studiesAntidepressant effects of ketamine in depressed patients
Berman R, Cappiello A, Anand A, Oren D, Heninger G, Charney D, Krystal J. Antidepressant effects of ketamine in depressed patients. Biological Psychiatry 2000, 47: 351-354. PMID: 10686270, DOI: 10.1016/s0006-3223(99)00230-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsDepressive Disorder, MajorDose-Response Relationship, DrugDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleGlutamic AcidHumansInjections, IntravenousKetamineMaleMiddle AgedPsychiatric Status Rating ScalesReceptors, N-Methyl-D-AspartateSeverity of Illness IndexConceptsMajor depressionN-methyl-D-aspartate receptor antagonistBrain glutamate systemDouble-blind trialDouble-blind conditionsTreatment of depressionMechanism of actionPlacebo infusionAntidepressant effectsIntravenous treatmentSingle doseReceptor antagonistDepressed patientsGlutamate systemDepressive symptomsPreclinical researchKetamine hydrochlorideDepressionPotential roleTest dayTreatment effectsPatientsKetamineSaline solutionTreatment
1999
Interactive effects of subanesthetic ketamine and haloperidol in healthy humans
Krystal J, D’Souza D, Karper L, Bennett A, Abi-Dargham A, Abi-Saab D, Cassello K, Bowers Jr. M, Vegso S, Heninger G, Charney D, Bowers M. Interactive effects of subanesthetic ketamine and haloperidol in healthy humans. Psychopharmacology 1999, 145: 193-204. PMID: 10463321, DOI: 10.1007/s002130051049.Peer-Reviewed Original ResearchConceptsHealthy subjectsOral administrationN-methyl-D-aspartate receptor antagonistIntravenous ketamine infusion