2021
The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis
Beck K, Hindley G, Borgan F, Ginestet C, McCutcheon R, Brugger S, Driesen N, Ranganathan M, D'Souza D, Taylor M, Krystal J, Howes O. The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis. BJPsych Open 2021, 7: s237-s237. PMCID: PMC8771247, DOI: 10.1192/bjo.2021.634.Peer-Reviewed Original ResearchBrief Psychiatric Rating ScaleEffects of ketaminePlacebo conditionPositive symptomsKetamine administrationKetamine effectsHealthy participantsHealthy volunteersNegative symptomsTherapeutic useAcute ketamine administrationAcute ketamine challengeMagnitude of symptomsStudy-level dataSub-group analysisPsychiatric Rating ScaleSchizophrenia-like symptomatologySchizophrenia-like symptomsMean change scoresNegative Syndrome ScalePositive psychotic symptomsSignificant increaseEffect sizeBolus dosesKetamine challenge
2020
Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers
Kantrowitz JT, Grinband J, Goff DC, Lahti AC, Marder SR, Kegeles LS, Girgis RR, Sobeih T, Wall MM, Choo TH, Green MF, Yang YS, Lee J, Horga G, Krystal JH, Potter WZ, Javitt DC, Lieberman JA. Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers. Neuropsychopharmacology 2020, 45: 1842-1850. PMID: 32403118, PMCID: PMC7608251, DOI: 10.1038/s41386-020-0706-z.Peer-Reviewed Original ResearchConceptsDorsal anterior cingulate cortexBrief Psychiatric Rating ScaleTS-134Target engagementHealthy volunteersMetabotropic glutamate receptor 2/3 agonistKetamine-induced psychotic symptomsBPRS positive symptomsDouble-blind conditionsProof of mechanismKetamine-induced changesAntipsychotic drug developmentTreatment of schizophreniaPsychiatric Rating ScaleAnterior cingulate cortexPrimary outcomeClinical symptomsGlutamatergic drugsGlutamate neurotransmissionTotal symptomsClinical assessmentLow dosePsychotic symptomsHigh dosePlacebo dataAssociation of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia
Beck K, Hindley G, Borgan F, Ginestet C, McCutcheon R, Brugger S, Driesen N, Ranganathan M, D’Souza D, Taylor M, Krystal JH, Howes OD. Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia. JAMA Network Open 2020, 3: e204693. PMID: 32437573, PMCID: PMC7243091, DOI: 10.1001/jamanetworkopen.2020.4693.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScalePlacebo conditionPositive symptomsNegative symptomsHealthy participantsMean differenceKetamine administrationPANSS scoresHealthy volunteersPsychotomimetic symptomsTherapeutic useAcute ketamine administrationAcute ketamine challengePlacebo-controlled studyEffect sizeMagnitude of symptomsStudy-level dataPsychiatric Rating ScaleMeta-Analyses (PRISMA) guidelinesPreferred Reporting ItemsAssociation of ketamineNegative Syndrome ScaleSignificant increaseAcute administrationBolus doses
2010
The 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
Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study
Stone JM, Erlandsson K, Arstad E, Squassante L, Teneggi V, Bressan RA, Krystal JH, Ell PJ, Pilowsky LS. Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study. Psychopharmacology 2008, 197: 401-408. PMID: 18176855, DOI: 10.1007/s00213-007-1047-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrief Psychiatric Rating ScaleDose-Response Relationship, DrugGuanidinesHumansInfusions, IntravenousIodine RadioisotopesKetamineMalePrefrontal CortexPsychoses, Substance-InducedReceptors, N-Methyl-D-AspartateSchizophreniaSingle-Blind MethodTomography, Emission-Computed, Single-PhotonConceptsBrief Psychiatric Rating ScaleVolume of distributionNMDA receptorsPsychotic symptomsN-methyl-D-aspartate receptorsKetamine-induced psychotic symptomsSingle photon emission tomographyNMDA receptor bindingEffects of ketamineNegative subscaleHealthy human controlsPsychiatric Rating ScaleNegative psychotic symptomsInferior frontal cortexKetamine administrationBolus infusionHealthy controls
2002
Ritanserin 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
1998
Naltrexone Augmentation of Neuroleptics in Schizophrenia
Sernyak M, Glazer W, Heninger G, Charney D, Woods S, Petrakis I, Krystal J, Price L. Naltrexone Augmentation of Neuroleptics in Schizophrenia. Journal Of Clinical Psychopharmacology 1998, 18: 248-251.. PMID: 9617985, DOI: 10.1097/00004714-199806000-00011.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleTotal BPRS scoreBPRS scoresNegative symptomsAddition of naltrexoneBPRS subscale scoresOngoing neuroleptic treatmentSingle-blind basisPlacebo-controlled trialSingle-blind fashionSubscale scoresBPRS total scorePsychiatric Rating ScaleDSM-III criteriaSubsequent treatmentRepeated-measures analysisNaltrexone augmentationNeuroleptic medicinesNeuroleptic regimenTransient exacerbationPlacebo armNeuroleptic treatmentClinical benefitRepeated-measures ANOVANaltrexoneInteractive 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
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
1993
m-Chlorophenylpiperazine Effects in Neuroleptic-Free Schizophrenic Patients: Evidence Implicating Serotonergic Systems in the Positive Symptoms of Schizophrenia
Krystal JH, Seibyl JP, Price LH, Woods SW, Heninger GR, Aghajanian GK, Charney DS. m-Chlorophenylpiperazine Effects in Neuroleptic-Free Schizophrenic Patients: Evidence Implicating Serotonergic Systems in the Positive Symptoms of Schizophrenia. JAMA Psychiatry 1993, 50: 624-635. PMID: 8102048, DOI: 10.1001/archpsyc.1993.01820200034004.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleHealthy subjectsPsychiatric Rating ScalePositive symptomsSchizophrenic patientsPatient groupDouble-blind randomized comparisonVeterans Affairs Medical CenterRating ScaleNeuroleptic-free schizophrenic patientsFirst patient groupSerotonin partial agonistPrincipal outcome variableVisual analog scaleBaseline prolactin levelsHigher baseline levelsSymptoms of schizophreniaAnalog scaleRandomized comparisonAnxiogenic responseSum of scoresProlactin levelsSerotonergic systemSerotonin functionHormone levels