2024
Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo‐controlled crossover laboratory study
Petrakis I, Nolen T, Vandergrift N, Hirsch S, Krystal J, De Vivo M, Sabados J, Pisani E, Newcomb J, Kosten T. Dexmedetomidine HCL (BXCL501) as a potential treatment for alcohol use disorder and comorbid PTSD: A phase 1b, placebo‐controlled crossover laboratory study. American Journal On Addictions 2024 PMID: 39152094, DOI: 10.1111/ajad.13637.Peer-Reviewed Original ResearchPathophysiology of posttraumatic stress disorderAlcohol use disorderSubjective effects of alcoholEffects of alcoholUse disorderComorbid alcohol use disorderAlcohol cue reactivityPosttraumatic stress disorderCrossover laboratory studyCue reactivityAlcohol cravingNoradrenergic dysregulationStress disorderBlood pressureSubjective effectsEthanol administrationClinically significant adverse effectsPharmacotherapeutic approachesTest daysReceptor agonistsPotential treatmentDouble-blind fashionCravingDrinking alcoholDisorders
2022
Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial
Krystal J, Kane J, Correll C, Walling D, Leoni M, Duvvuri S, Patel S, Chang I, Iredale P, Frohlich L, Versavel S, Perry P, Sanchez R, Renger J. Emraclidine, a novel positive allosteric modulator of cholinergic M4 receptors, for the treatment of schizophrenia: a two-part, randomised, double-blind, placebo-controlled, phase 1b trial. The Lancet 2022, 400: 2210-2220. PMID: 36528376, DOI: 10.1016/s0140-6736(22)01990-0.Peer-Reviewed Original ResearchConceptsTreatment of schizophreniaPositive allosteric modulatorsAdverse eventsUS sitesAllosteric modulatorsFavorable side effect profileMini International Neuropsychiatric InterviewNovel positive allosteric modulatorReceptor positive allosteric modulatorExtrapyramidal symptom assessmentMultiple ascending dosesCommon adverse eventsPhase 1b trialPlacebo-controlled studySide effect profileInternational Neuropsychiatric InterviewCohort of participantsAscending dosesSafety populationPrimary endpointBlood pressureM4 receptorsTreatment initiationDaily treatmentOral dosesLong-term safety of ketamine and esketamine in treatment of depression
Nikayin S, Murphy E, Krystal JH, Wilkinson ST. Long-term safety of ketamine and esketamine in treatment of depression. Expert Opinion On Drug Safety 2022, 21: 777-787. PMID: 35416105, DOI: 10.1080/14740338.2022.2066651.Peer-Reviewed Original ResearchConceptsLong-term safetyClinical trialsRacemic ketamineLong-term safety effectsRapid-acting antidepressant effectsLower urinary tract symptomsKetamine/esketamineTreatment-resistant depressionUrinary tract symptomsCommon side effectsTreatment of depressionLong-term impairmentElevated heart ratePhase three clinical trialsTract symptomsAntidepressant effectsBlood pressureIncreased riskBladder pathologyEsketamineHeart ratePsychiatric disordersSide effectsCognitive impairmentHigh doses
2019
Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET
Holmes SE, Gallezot JD, Davis MT, DellaGioia N, Matuskey D, Nabulsi N, Krystal JH, Javitch JA, DeLorenzo C, Carson RE, Esterlis I. Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 2254-2264. PMID: 31744389, PMCID: PMC7585925, DOI: 10.1177/0271678x19886316.Peer-Reviewed Original ResearchConceptsEffects of ketamineKetamine infusionGlutamate transmissionMetabotropic glutamate receptor 5Ketamine-induced effectsKetamine-induced changesGlutamate receptor 5Promising treatment targetDrug challenge studiesTwo-tissue compartment modelMGluR5 radioligandBlood pressureMGluR5 availabilityBaseline scanOutcome measuresHealthy subjectsHeart ratePsychiatric disordersReceptor 5Modulatory effectsMGluR5Treatment targetsChallenge studiesArterial input functionChallenge paradigm
2002
Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients
Stine SM, Southwick SM, Petrakis IL, Kosten TR, Charney DS, Krystal JH. Yohimbine-induced withdrawal and anxiety symptoms in opioid-dependent patients. Biological Psychiatry 2002, 51: 642-651. PMID: 11955464, DOI: 10.1016/s0006-3223(01)01292-6.Peer-Reviewed Original ResearchConceptsOpioid-dependent patientsBlood pressureMethadone patientsOpioid dependenceHPA axis perturbationsPlacebo-controlled studyDiastolic blood pressureSystolic blood pressureMethadone-maintained patientsSymptom scale scoresSynaptic noradrenalineOpioid withdrawalPostsynaptic effectsMHPG levelsAbstinence symptomsAdrenal axisOpioid drugsYohimbine effectNoradrenergic regulationHealthy volunteersHeart ratePhysiologic measuresPatientsCortisol levelsScale score
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 veteransYohimbine
1996
Noradrenergic mechanisms in stress and anxiety: II. Clinical studies
Bremner J, Krystal J, Southwick S, Charney D. Noradrenergic mechanisms in stress and anxiety: II. Clinical studies. Synapse 1996, 23: 39-51. PMID: 8723134, DOI: 10.1002/(sici)1098-2396(199605)23:1<39::aid-syn5>3.0.co;2-i.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderBlood pressureNoradrenergic functionHeart rateNoradrenergic systemClinical studiesAdrenergic receptorsPanic disorderAnxiety disordersGrowth hormone responseMeasurement of norepinephrineNorepinephrine responseNoradrenergic mechanismsBaseline norepinephrineNoradrenergic responsivenessPharmacological challengeCatecholaminergic functionHormone responseTraumatic remindersPatientsAcute stressorStress disorderNorepinephrineBaseline measuresConsistent finding
1995
Noradrenergic response to acute ethanol administration in heathly subjects: comparison with intravenous yohimbine
McDougle C, Price L, Heninger G, Krystal J, Charney D. Noradrenergic response to acute ethanol administration in heathly subjects: comparison with intravenous yohimbine. Psychopharmacology 1995, 118: 127-135. PMID: 7617798, DOI: 10.1007/bf02245830.Peer-Reviewed Original ResearchConceptsAcute ethanol administrationEthanol administrationPlasma MHPGIntravenous yohimbineBlood pressureNE turnoverSystolic blood pressureAlpha2-adrenergic receptorsPlacebo-controlled designBlood pressure measurementsEthanol-induced increaseHealthy human subjectsClear additive effectSubjective measuresNE metabolismNoradrenergic responsesNorepinephrine metaboliteCombined administrationMHPG responsePlasma levelsPharmacokinetic effectsOral administrationIntravenous administrationAnxiogenic effectsEthanol intoxication
1993
Abnormal Noradrenergic Function in Posttraumatic Stress Disorder
Southwick SM, Krystal JH, Morgan CA, Johnson D, Nagy LM, Nicolaou A, Heninger GR, Charney DS. Abnormal Noradrenergic Function in Posttraumatic Stress Disorder. JAMA Psychiatry 1993, 50: 266-274. PMID: 8466387, DOI: 10.1001/archpsyc.1993.01820160036003.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderYohimbine-induced panic attacksUncontrollable stressStress disorderYohimbine-induced increasesSystolic blood pressureSubgroup of patientsHealthy male subjectsCore PTSD symptomsCardiovascular effectsBlood pressureMale patientsPathophysiological relationshipNoradrenergic functionPreclinical dataNeurobiological sequelaeHealthy subjectsHeart rateNeuronal regulationPanic disorderMale subjectsNeuronal functionPanic attacksPatientsYohimbine hydrochloride
1992
Dose-response relationship for oral idazoxan effects in healthy human subjects: comparison with oral yohimbine
Krystal J, McDougle C, Woods S, Price L, Heninger G, Charney D. Dose-response relationship for oral idazoxan effects in healthy human subjects: comparison with oral yohimbine. Psychopharmacology 1992, 108: 313-319. PMID: 1355923, DOI: 10.1007/bf02245117.Peer-Reviewed Original ResearchConceptsHealthy subjectsDiastolic blood pressureΑ2-adrenergic receptorsSymptom scale scoresHealthy human subjectsDose-response relationshipIdazoxan doseBlood pressureOral yohimbineNorepinephrine metabolitePlasma levelsMedication effectsOral administrationPlasma MHPGPhysiologic indicesNeuroendocrine responsesΑ2 antagonistAdrenergic receptorsCortisol levelsScale scorePlasma cortisolYohimbineIdazoxanAnxiety statesReceptor specificity
1991
Behavioral, biochemical, and cardiovascular responses to the benzodiazepine receptor antagonist flumazenil in panic disorder
Woods S, Charney D, Silver J, Krystal J, Heninger G. Behavioral, biochemical, and cardiovascular responses to the benzodiazepine receptor antagonist flumazenil in panic disorder. Psychiatry Research 1991, 36: 115-127. PMID: 1850142, DOI: 10.1016/0165-1781(91)90124-8.Peer-Reviewed Original ResearchConceptsAntagonist flumazenilAnxiolytic effectsBenzodiazepine receptor antagonist flumazenilReceptor antagonist flumazenilDose of flumazenilVisual analog scaleBenzodiazepine receptor functionBZR inverse agonistsSignificant anxiolytic effectSeparate test daysPlacebo capsulesBlood pressureAnalog scaleCardiovascular responsesDisorder patientsHeart rateFlumazenilCrossover designPanic patientsPanic disorderPlasma cortisolBaseline levelsPanic attacksPlaceboReceptor function
1990
Opioid antagonist challenges in buprenorphine maintained patients
Kosten T, Krystal J, Charney D, Price L, Morgan C, Kleber H. Opioid antagonist challenges in buprenorphine maintained patients. Drug And Alcohol Dependence 1990, 25: 73-78. PMID: 2323312, DOI: 10.1016/0376-8716(90)90144-4.Peer-Reviewed Original ResearchConceptsSublingual buprenorphine treatmentBlood pressure increaseDouble-blind placeboOpioid withdrawal symptomsBlind placeboIntravenous naloxoneNaltrexone challengeOral naltrexoneLast doseBlood pressureBuprenorphine treatmentPlacebo substitutionMHPG levelsWithdrawal symptomsPlacebo challengeSignificant symptomsAntagonist challengeBuprenorphinePatientsPlaceboNaloxoneSymptomsNaltrexoneDoseMonths