2020
Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity
Preller KH, Duerler P, Burt JB, Ji JL, Adkinson B, Stämpfli P, Seifritz E, Repovš G, Krystal JH, Murray JD, Anticevic A, Vollenweider FX. Psilocybin Induces Time-Dependent Changes in Global Functional Connectivity. Biological Psychiatry 2020, 88: 197-207. PMID: 32111343, DOI: 10.1016/j.biopsych.2019.12.027.Peer-Reviewed Original ResearchConceptsFunctional connectivityBaseline connectivityResting-state functional connectivityGlobal functional connectivityBrain-wide connectivityHealthy human participantsPersonalized medicine approachPeak effectUse of psilocybinMechanism of actionSerotonin 2ATime-dependent mannerCrossover studyPredictive markerPsychedelic treatmentMedicine approachReceptor systemSensory regionsClinical contextTime pointsAssociative regionsDifferent test daysAdministrationTest dayTime-dependent changes
2015
Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine
Ahn KH, Sewell A, Elander J, Pittman B, Ranganathan M, Gunduz-Bruce H, Krystal J, D'Souza DC. Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine. Neuropsychopharmacology 2015, 40: 2822-2831. PMID: 25953357, PMCID: PMC4864658, DOI: 10.1038/npp.2015.132.Peer-Reviewed Original ResearchConceptsGABA deficitHealthy subjectsPsychotomimetic effectsIntravenous infusionSchizophrenia patientsPANSS positive symptoms subscaleDouble-blind crossover designStriatal dopamine releasePositive symptom subscaleAdministration of drugsDose of AMPHPartial inverse agonistSubclinical responsePharmacokinetic interactionsSubthreshold doseDopamine releaseBenzodiazepine receptorsSymptom subscalesCrossover designCADSS scoresPositive symptomsAMPHInverse agonistSubjective effectsTest day
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
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
2006
Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects
Neumeister A, Carson R, Henry S, Planeta-Wilson B, Binneman B, Maguire RP, Luckenbaugh DA, D'Souza C, Krystal JH, Frost JJ. Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects. Journal Of Clinical Psychopharmacology 2006, 26: 595-599. PMID: 17110816, DOI: 10.1097/01.jcp.0000245558.14284.aa.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntipsychotic AgentsBehaviorBrainBrain MappingCluster AnalysisCross-Over StudiesDouble-Blind MethodFemaleFluorodeoxyglucose F18GlycineHumansInfusions, IntravenousMagnetic Resonance ImagingMaleNeuropsychological TestsPositron-Emission TomographyRadiopharmaceuticalsReference ValuesSerineConceptsN-methyl-D-aspartate receptor functionReceptor functionRegional cerebral metabolic rateAdministration of glycineCerebral metabolic effectsMagnetic resonance imaging studyPositron emission tomography studyHealthy control subjectsNMDA receptor functionCerebral metabolic rateEmission tomography studiesTest dayHealthy human subjectsResonance imaging studySignificant reductionPositron emission tomographyDorsolateral prefrontal cortexIntravenous glycinePlacebo infusionCerebral metabolismPatient populationControl subjectsGlycine administrationGlycine infusionIntravenous administration
2005
Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function
Krystal JH, Perry EB, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A, Cooper TB, MacDougall L, Abi-Saab W, D’Souza D. Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function. JAMA Psychiatry 2005, 62: 985-995. PMID: 16143730, DOI: 10.1001/archpsyc.62.9.985.Peer-Reviewed Original Research
2004
Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects
Krystal JH, Abi-Saab W, Perry E, D’Souza D, Liu N, Gueorguieva R, McDougall L, Hunsberger T, Belger A, Levine L, Breier A. Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology 2004, 179: 303-309. PMID: 15309376, DOI: 10.1007/s00213-004-1982-8.Peer-Reviewed Original ResearchConceptsGroup II metabotropic glutamate receptor agonistMetabotropic glutamate receptor agonistHealthy human subjectsNMDA glutamate receptor antagonistGlutamate receptor agonistsGlutamate receptor antagonistsTest dayCognitive effectsPerceptual changesKetamine infusionReceptor antagonistReceptor agonistDysphoric moodMemory impairmentBehavioral consequencesSignificant dose-related improvementGroup II mGluR agonistReceptor functionHuman subjectsMemoryNegative symptomsDose-related improvementNMDA receptor functionPreliminary evidenceDisruptive effects
2002
The Effect of Tryptophan Depletion on Alcohol Self‐Administration in Non‐Treatment‐Seeking Alcoholic Individuals
Petrakis IL, Buonopane A, O'Malley S, Cermik O, Trevisan L, Boutros NN, Limoncelli D, Krystal JH. The Effect of Tryptophan Depletion on Alcohol Self‐Administration in Non‐Treatment‐Seeking Alcoholic Individuals. Alcohol Clinical And Experimental Research 2002, 26: 969-975. PMID: 12170105, DOI: 10.1111/j.1530-0277.2002.tb02629.x.Peer-Reviewed Original ResearchConceptsTest sessionsActive tryptophan depletionSelf-reported cravingTryptophan depletionFavorite alcoholic beverageCue exposure sessionsAmount of alcoholAmino acid drinkSelf-administration paradigmAlcohol-dependent individualsAlcohol Self-AdministrationAlcohol use disorderDependence of alcoholNeurobiological mechanismsExposure sessionsSubjective intoxicationBlood alcohol levelsPriming drinkAlcohol useAcid drinkUse disordersAlcoholic individualsAlcohol dependenceCravingTest dayRitanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms
Abi-Saab W, Seibyl JP, D'Souza C, Karper LP, Gueorgueva R, Abi-Dargham A, Wong ML, Rajhans S, Erdos JP, Heninger GR, Charney DS, Krystal JH. Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms. Psychopharmacology 2002, 162: 55-62. PMID: 12107618, DOI: 10.1007/s00213-002-1057-7.Peer-Reviewed Original ResearchConceptsReceptor antagonismSchizophrenic patientsNeuroleptic-free schizophrenic patientsBrief Psychiatric Rating ScaleDouble-blind conditionsPsychiatric Rating ScaleTest dayRitanserin pretreatmentIntravenous infusionReceptor modulationAntipsychotic activityMale inpatientsReceptor stimulationPlasma prolactinCortisol levelsSchizoaffective disorderSchizophrenia symptomsPositive symptomsNegative symptomsRandomized orderPatientsRating ScaleBehavioral activationSymptomsRitanserin
2001
Effect of Tryptophan Depletion on Alcohol Cue‐Induced Craving in Abstinent Alcoholic Patients
Petrakis I, Trevisan L, Boutros N, Limoncelli D, Cooney N, Krystal J. Effect of Tryptophan Depletion on Alcohol Cue‐Induced Craving in Abstinent Alcoholic Patients. Alcohol Clinical And Experimental Research 2001, 25: 1151-1155. PMID: 11505046, DOI: 10.1111/j.1530-0277.2001.tb02329.x.Peer-Reviewed Original ResearchConceptsCue-induced cravingAlcohol-dependent patientsTryptophan depletionAlcohol cue-induced cravingDouble-blind fashionPlasma free tryptophanAbstinent alcoholic patientsAmino acid drinkActive tryptophan depletionAlcoholic patientsSerotonin synthesisAcid drinkSober alcoholicsAlcoholic individualsPrecursor tryptophanCue exposurePatientsAlcohol useAbstinent alcoholic individualsCravingFree tryptophanAlcohol cuesTest dayGreater increaseSimilar drinks
2000
IV glycine and oral d-cycloserine effects on plasma and CSF amino acids in healthy humans
D’Souza D, Gil R, Cassello K, Morrissey K, Abi-Saab D, White J, Sturwold R, Bennett A, Karper L, Zuzarte E, Charney D, Krystal J. IV glycine and oral d-cycloserine effects on plasma and CSF amino acids in healthy humans. Biological Psychiatry 2000, 47: 450-462. PMID: 10704956, DOI: 10.1016/s0006-3223(99)00133-x.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAdministration, OralAdultAmino AcidsAntimetabolitesBiological AvailabilityCycloserineDose-Response Relationship, DrugDouble-Blind MethodFemaleGlycineHumansInjections, IntravenousMaleMiddle AgedNeuropsychological TestsPsychiatric Status Rating ScalesReceptors, GlycineReceptors, N-Methyl-D-AspartateReflex, StartleSerineConceptsAcoustic startle responseN-methyl-D-aspartate (NMDA) glutamate receptorsD-cycloserineStartle responseCentral nervous system effectsTest dayCSF glycine levelsOral D-cycloserineCSF amino acidsNervous system effectsDouble-blind conditionsCognitive test performanceD-cycloserine effectsHealthy human subjectsCentral bioavailabilityIntravenous glycineLumbar punctureSecond test dayGlycine administrationModulates neurotransmissionGlycine levelsGlutamate receptorsCoagonist siteCerebrospinal fluidHealthy humansAntidepressant 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 solutionTreatmentDissociation of ketamine effects on rule acquisition and rule implementation: possible relevance to NMDA receptor contributions to executive cognitive functions
Krystal J, Bennett A, Abi-Saab D, Belger A, Karper L, D’Souza D, Lipschitz D, Abi-Dargham A, Charney D. Dissociation of ketamine effects on rule acquisition and rule implementation: possible relevance to NMDA receptor contributions to executive cognitive functions. Biological Psychiatry 2000, 47: 137-143. PMID: 10664830, PMCID: PMC10060085, DOI: 10.1016/s0006-3223(99)00097-9.Peer-Reviewed Original ResearchConceptsExecutive cognitive functionSecond test dayPerseverative errorsWCST performanceCognitive functionTest daySecond studyExecutive componentTask repetitionAltered perceptionWCSTNMDA antagonist ketamineNegative symptomsFrontal cortexRule acquisitionTest changesFirst studySingle repetitionKetamine effectsRepetitionTotal errorDistractibilityReceptor contributionNMDA receptor contributionRecall
1998
Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans
Krystal J, Karper L, Bennett A, D’Souza D, Abi-Dargham A, Morrissey K, Abi-Saab D, Bremner J, Bowers Jr. M, Suckow R, Stetson P, Heninger G, Charney D. Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans. Psychopharmacology 1998, 135: 213-229. PMID: 9498724, DOI: 10.1007/s002130050503.Peer-Reviewed Original ResearchConceptsWisconsin Card Sorting TestClinician-Administered Dissociative States ScalePerceptual alterationsAmnestic effectsInteractive effectsCard Sorting TestBrief Psychiatric Rating ScaleAttention impairmentSorting TestPerceptual effectsProverb interpretationEmotional distressDissociative effectsCortical impairmentNegative symptomsState scaleBehavioral effectsTest dayPsychiatric Rating ScaleLorazepam 2ImpairmentRating ScaleSubanesthetic ketamineHealthy humansPlacebo 2
1997
Noradrenergic and Serotonergic Function in Posttraumatic Stress Disorder
Southwick SM, Krystal JH, Bremner JD, Morgan CA, Nicolaou AL, Nagy LM, Johnson DR, Heninger GR, Charney DS. Noradrenergic and Serotonergic Function in Posttraumatic Stress Disorder. JAMA Psychiatry 1997, 54: 749-758. PMID: 9283511, DOI: 10.1001/archpsyc.1997.01830200083012.Peer-Reviewed Original ResearchConceptsYohimbine-induced panic attacksPosttraumatic stress disorderPanic attacksCardiovascular effectsCardiovascular measurementsStress disorderYohimbine hydrochloridePTSD symptomsDiastolic blood pressureDouble-blind fashionSeparate test daysGreater increaseBlood pressureIntravenous infusionSerotonergic functionNoradrenergic activitySerotonergic systemNoradrenergic systemHealthy subjectsSerotonergic activityPatientsDifferent patientsTest dayCombat veteransYohimbineEvidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-Chlorophenylpiperazine (mCPP)
Krystal J, Webb E, Grillon C, Cooney N, Casal L, Morgan III. C, Southwick S, Davis M, Charney D. Evidence of acoustic startle hyperreflexia in recently detoxified early onset male alcoholics: modulation by yohimbine and m-Chlorophenylpiperazine (mCPP). Psychopharmacology 1997, 131: 207-215. PMID: 9203230, DOI: 10.1007/s002130050285.Peer-Reviewed Original ResearchConceptsHealthy subjectsAcoustic startle responseEthanol withdrawalStartle responseStartle magnitudeStartle amplitudeRandomized orderAcoustic startle magnitudeChronic alcoholic patientsSerotonin partial agonistDouble-blind conditionsAcoustic startle amplitudeNumber of episodesMale healthy subjectsΑ2-adrenergic antagonistTest dayMale patientsPlacebo dayAlcoholic patientsIntravenous infusionNoradrenergic functionYohimbine effectAlcohol detoxificationDrug infusionPreclinical studies
1994
Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans: Psychotomimetic, Perceptual, Cognitive, and Neuroendocrine Responses
Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB, Charney DS. Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans: Psychotomimetic, Perceptual, Cognitive, and Neuroendocrine Responses. JAMA Psychiatry 1994, 51: 199-214. PMID: 8122957, DOI: 10.1001/archpsyc.1994.03950030035004.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlood PressureCognitionDissociative DisordersDose-Response Relationship, DrugDouble-Blind MethodFemaleFrontal LobeHomovanillic AcidHumansHydrocortisoneKetamineMaleMethoxyhydroxyphenylglycolNeuropsychological TestsPerceptionProlactinPsychiatric Status Rating ScalesPsychoses, Substance-InducedPulseReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologyConceptsWisconsin Card Sorting TestCard Sorting TestMini-Mental State ExaminationSorting TestNegative symptomsTests of vigilanceVerbal fluency taskDissociative statesState ExaminationFrontal cortical dysfunctionPsychosis Proneness ScalesClinician-Administered Dissociative States ScaleWord recallImmediate recallVerbal fluencyFluency taskVigilance taskCognitive deficitsCognitive functionRecallState scaleBrief Psychiatric Rating ScaleCortical dysfunctionTest dayPsychiatric Rating Scale