2012
Feasibility, Safety, and Efficacy of the Combination of D-Serine and Computerized Cognitive Retraining in Schizophrenia: An International Collaborative Pilot Study
D'Souza DC, Radhakrishnan R, Perry E, Bhakta S, Singh NM, Yadav R, Abi-Saab D, Pittman B, Chaturvedi SK, Sharma MP, Bell M, Andrade C. Feasibility, Safety, and Efficacy of the Combination of D-Serine and Computerized Cognitive Retraining in Schizophrenia: An International Collaborative Pilot Study. Neuropsychopharmacology 2012, 38: 492-503. PMID: 23093223, PMCID: PMC3547200, DOI: 10.1038/npp.2012.208.Peer-Reviewed Original ResearchConceptsCognitive retrainingCognitive deficitsVerbal Working MemoryCognitive remediation strategiesAttention/vigilanceBasic information processingIndividual test performanceGlobal cognitive indexWorking memoryD-serineCognitive indicesCombination of pharmacotherapyTest performanceInformation processingMulticenter international clinical trialParallel group designSchizophrenia subjectsCollaborative pilot studyInternational clinical trialsUS samplePreliminary findingsCombination pharmacotherapySchizophreniaClinical trialsOutcome measuresNaltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans
Ranganathan M, Carbuto M, Braley G, Elander J, Perry E, Pittman B, Radhakrishnan R, Sewell RA, D'Souza DC. Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans. The International Journal Of Neuropsychopharmacology 2012, 15: 1251-1264. PMID: 22243563, DOI: 10.1017/s1461145711001830.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAttentionBehaviorCognitionCognition DisordersDouble-Blind MethodDronabinolDrug InteractionsEuphoriaFemaleHallucinogensHumansInhibition, PsychologicalInjections, IntravenousMaleMarijuana AbuseMemoryMental RecallMiddle AgedNaltrexoneNarcotic AntagonistsOrientationPerceptionPsychoses, Substance-InducedRecognition, PsychologyRewardYoung AdultConceptsCognitive effectsHealthy human subjectsPerceptual alterationsHuman subjectsTHC effectsCognitive impairmentΔ9-tetrahydrocannabinolActive naltrexoneDouble-blind mannerTest dayPsychotomimetic effectsPreclinical evidenceMOR antagonistΜ-opioidCB1R agonistPsychiatric illnessPrecise natureHealthy humansDrug AdministrationReceptor systemNaltrexoneEffect of pretreatmentAnxietyPlaceboTHC
2011
Preliminary Findings on the Interactive Effects of IV Ethanol and IV Nicotine on Human Behavior and Cognition: A Laboratory Study
Ralevski E, Perry EB, D’Souza D, Bufis V, Elander J, Limoncelli D, Vendetti M, Dean E, Cooper TB, McKee S, Petrakis I. Preliminary Findings on the Interactive Effects of IV Ethanol and IV Nicotine on Human Behavior and Cognition: A Laboratory Study. Nicotine & Tobacco Research 2011, 14: 596-606. PMID: 22180582, PMCID: PMC6281082, DOI: 10.1093/ntr/ntr258.Peer-Reviewed Original ResearchConceptsRey Auditory Verbal Learning TaskAuditory Verbal Learning TaskVerbal learning taskAcute intravenous alcoholSubjective alcohol effectsBiphasic Alcohol Effects ScaleAlcohol-induced deficitsAlcohol-induced impairmentDoses of alcoholActive nicotineInteractive effectsTest dayCognitive inhibitionVerbal learningCognitive performanceLearning taskSubjective intoxicationAlcohol effectsHuman behaviorNicotine effectsIntravenous alcoholAlcohol infusionManner oneSubjective effectsCognitionThe safety of studies with intravenous Δ9-tetrahydrocannabinol in humans, with case histories
Carbuto M, Sewell RA, Williams A, Forselius-Bielen K, Braley G, Elander J, Pittman B, Schnakenberg A, Bhakta S, Perry E, Ranganathan M, D’Souza D, The Yale THC Study Group. The safety of studies with intravenous Δ9-tetrahydrocannabinol in humans, with case histories. Psychopharmacology 2011, 219: 885-896. PMID: 21845389, DOI: 10.1007/s00213-011-2417-y.Peer-Reviewed Original ResearchConceptsAdverse eventsPost-study periodCareful subject selectionMinor adverse eventsPhysical adverse eventsFrequent side effectsLong-term followCannabinoid receptor systemFaster infusion rateCannabinoid receptor ligandsIntravenous THCPlacebo infusionCannabinoid systemInfusion rateStudy participationSide effectsAbuse liabilityHigh dosesReceptor systemΔ9-tetrahydrocannabinolInfusionPsychoactive effectsReceptor ligandsTest daySubjects
2010
Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler
Esterlis I, Mitsis EM, Batis JC, Bois F, Picciotto MR, Stiklus SM, Kloczynski T, Perry E, Seibyl JP, McKee S, Staley JK, Cosgrove KP. Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler. The International Journal Of Neuropsychopharmacology 2010, 14: 389-398. PMID: 21029513, PMCID: PMC3510008, DOI: 10.1017/s1461145710001227.Peer-Reviewed Original ResearchConceptsNicotine inhalerWithdrawal symptomsReceptor occupancyTobacco smokingLow nicotine cigarettesAdministration of nicotineHigh receptor occupancyDoses of nicotineNicotinic acetylcholine receptorsInhaler useTobacco smokersBaseline scanRegular cigarettesInhalerConstant infusionAcetylcholine receptorsSPECT studiesCigarettesSymptomsBeta 2Significant decreaseNicotineSignificant differencesSmokingNAChRsClinical significance of neurological soft signs in schizophrenia: Factor analysis of the Neurological Evaluation Scale
Sewell RA, Perry EB, Karper LP, Bell MD, Lysaker P, Goulet JL, Brenner L, Erdos J, d'Souza DC, Seibyl JP, Krystal JH. Clinical significance of neurological soft signs in schizophrenia: Factor analysis of the Neurological Evaluation Scale. Schizophrenia Research 2010, 124: 1-12. PMID: 20855185, DOI: 10.1016/j.schres.2010.08.036.Peer-Reviewed Original ResearchConceptsNeurological Evaluation ScaleAbnormal Involuntary Movement ScaleDigit Symbol Substitution TaskWisconsin Card Sorting TestNeurologic deficitsClinical significanceExtrapyramidal Symptom Rating ScaleMore extrapyramidal symptomsBarnes Akathisia ScaleDetailed clinical assessmentNeurological soft signsSymptom Rating ScaleNegative Syndrome ScaleHigher AIMS scoresEvaluation ScaleNeurological deficitsExtrapyramidal symptomsClinical correlatesDeficit syndrome schizophreniaClinical evaluationClinical assessmentAIMS scoresLower PANSSMovement ScaleSoft signsSPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals
Esterlis I, Cosgrove KP, Petrakis IL, McKee SA, Bois F, Krantzler E, Stiklus SM, Perry EB, Tamagnan GD, Seibyl JP, Krystal JH, Staley JK. SPECT imaging of nicotinic acetylcholine receptors in nonsmoking heavy alcohol drinking individuals. Drug And Alcohol Dependence 2010, 108: 146-150. PMID: 20074869, PMCID: PMC2871672, DOI: 10.1016/j.drugalcdep.2009.12.006.Peer-Reviewed Original ResearchConceptsDrinks/occasionNicotinic acetylcholine receptorsControl nonsmokersAcetylcholine receptorsHeavy drinkersHeavy drinkingLast alcoholic beverageHeavy alcohol drinkersHeavy alcoholSingle photon emissionSeverity of drinkingEffect of ageTobacco smokingAlcohol drinkersAlcohol drinkingCommon neural substrateNonsmokersAlcohol consumptionReceptor availabilityLarger studyAlcohol drinksAlcohol use behaviorsAddictive disordersDrinkersNeural substrates
2009
GABAA‐benzodiazepine receptor availability in smokers and nonsmokers: Relationship to subsyndromal anxiety and depression
Esterlis I, Cosgrove KP, Batis JC, Bois F, Kloczynski TA, Stiklus SM, Perry E, Tamagnan GD, Seibyl JP, Makuch R, Krishnan‐Sarin S, O'Malley S, Staley JK. GABAA‐benzodiazepine receptor availability in smokers and nonsmokers: Relationship to subsyndromal anxiety and depression. Synapse 2009, 63: 1089-1099. PMID: 19642218, PMCID: PMC2778224, DOI: 10.1002/syn.20688.Peer-Reviewed Original ResearchConceptsSpielberger State-Trait Anxiety IndexState-Trait Anxiety IndexDepressive symptomsSubsyndromal anxietyAnxiety symptomsPain toleranceReceptor availabilityAbstinent tobacco smokersSex-matched nonsmokersSingle photon emissionPain symptomsHealthy ageSmoking statusTobacco smokersSubsyndromal depressionAbstinent smokersVulnerable smokersCold pressor taskNonsmokersGamma-aminobutyricEpidemiology ScaleSmokersAcute abstinenceBrain areasSymptomsβ2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking
Cosgrove KP, Batis J, Bois F, Maciejewski PK, Esterlis I, Kloczynski T, Stiklus S, Krishnan-Sarin S, O’Malley S, Perry E, Tamagnan G, Seibyl JP, Staley JK. β2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking. JAMA Psychiatry 2009, 66: 666-676. PMID: 19487632, PMCID: PMC2796827, DOI: 10.1001/archgenpsychiatry.2009.41.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzetidinesBrainBrain MappingDominance, CerebralFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedIodine RadioisotopesMagnetic Resonance ImagingMaleMiddle AgedNicotineReceptors, NicotinicSmokingSmoking CessationSubstance Withdrawal SyndromeTobacco Use DisorderTomography, Emission-Computed, Single-PhotonConceptsWeeks of abstinenceTobacco smokingTobacco smokersAbstinent tobacco smokersAge-matched nonsmokersMagnetic resonance imaging studyMain outcome measuresCourse of abstinenceResonance imaging studyNicotinic acetylcholine receptorsMonths of abstinenceSingle photon emissionDays of abstinenceIA SPECTNonsmoker levelsClinical featuresTobacco cessationNicotine withdrawalTomography scanOutcome measuresSPECT scansSmokersReceptor availabilityAcetylcholine receptorsSmoking
2008
The effects of cannabinoids on serum cortisol and prolactin in humans
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J, D’Souza D. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology 2008, 203: 737. PMID: 19083209, PMCID: PMC2863108, DOI: 10.1007/s00213-008-1422-2.Peer-Reviewed Original ResearchConceptsPlasma prolactin levelsPlasma cortisol levelsProlactin levelsNeuroendocrine effectsCannabis exposureHealthy controlsNeuroendocrine functionHormonal levelsCortisol levelsFrequent usersChronic cannabis exposureHealthy control subjectsDose-related increaseEffects of cannabinoidsBaseline hormonal levelsDose-related effectsDevelopment of toleranceLimited dose-response dataDose-dependent mannerBlunted increaseMultiple dosesControl subjectsSerum cortisolHormone levelsPlasma cortisolPreliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans
D’Souza D, Pittman B, Perry E, Simen A. Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans. Psychopharmacology 2008, 202: 569. PMID: 18807247, PMCID: PMC2791800, DOI: 10.1007/s00213-008-1333-2.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorBDNF levelsBrain-derived neurotrophic factor levelsNeurotrophic factor levelsSerum BDNF levelsΔ9-THCEffects of cannabinoidsΔ9-THC administrationSpatial memory impairmentBasal BDNF levelsResultsΔ9-THCPlacebo administrationPrincipal active componentNeurotrophic factorControl subjectsPsychotomimetic effectsHealthy controlsCannabinoid effectsIntravenous administrationAltered neurodevelopmentPreclinical studiesHigh riskConsequence of exposureChronic exposureMemory impairmentEffects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Δ-9-tetrahydrocannabinol in humans
D’Souza D, Braley G, Blaise R, Vendetti M, Oliver S, Pittman B, Ranganathan M, Bhakta S, Zimolo Z, Cooper T, Perry E. Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Δ-9-tetrahydrocannabinol in humans. Psychopharmacology 2008, 198: 587-603. PMID: 18228005, PMCID: PMC2878815, DOI: 10.1007/s00213-007-1042-2.Peer-Reviewed Original ResearchConceptsPerceptual alterationsPsychotomimetic effectsCambridge taskRecall deficitsVerbal recallSample taskCognitive effectsMemory impairmentCognitive impairmentSubjective effectsPreclinical literatureBehavioral effectsTaskD2 receptor mechanismsEffects of haloperidolFrequent usersDopaminergic systemHaloperidol pretreatmentImpairmentDistractibilityRecallResultsConsistentSpectrum of effectsRandom orderDeficitsBlunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent Users of Cannabis
D'Souza DC, Ranganathan M, Braley G, Gueorguieva R, Zimolo Z, Cooper T, Perry E, Krystal J. Blunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent Users of Cannabis. Neuropsychopharmacology 2008, 33: 2505-2516. PMID: 18185500, PMCID: PMC3799954, DOI: 10.1038/sj.npp.1301643.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmnesiaAttentionBrainDose-Response Relationship, DrugDouble-Blind MethodDronabinolDrug Administration ScheduleDrug ToleranceFemaleHallucinationsHallucinogensHumansHydrocortisoneMaleMarijuana AbuseMiddle AgedPerceptual DisordersProlactinPsychoses, Substance-InducedTachycardiaYoung AdultConceptsAmnestic effectsPerceptual alterationsDelta-9-TetrahydrocannabinolCannabis useSubjective effectsFrequent usersCannabisEffects of cannabinoidsIllicit substancesPsychotomimetic effectsEuphoric effectsHealthy controlsHealthy individualsMemoryImpairingPsychosisDose-related effectsIndividualsCortisolPsychotomimeticsAttentionPeopleUsersPlacebo-controlled studyEffect
2007
Absence of Significant Interactive Effects of High‐Dose d‐Cycloserine and Ethanol in Healthy Human Subjects: Preliminary Insights Into Ethanol Actions at the GlycineB Site of NMDA Glutamate Receptors
Trevisan L, Petrakis IL, Pittman B, Gueorguieva R, D’Souza D, Perry E, Limoncelli D, Krystal JH. Absence of Significant Interactive Effects of High‐Dose d‐Cycloserine and Ethanol in Healthy Human Subjects: Preliminary Insights Into Ethanol Actions at the GlycineB Site of NMDA Glutamate Receptors. Alcohol Clinical And Experimental Research 2007, 32: 36-42. PMID: 18028532, DOI: 10.1111/j.1530-0277.2007.00543.x.Peer-Reviewed Original ResearchConceptsCo-agonist siteHealthy human subjectsEthanol administrationD-cycloserineHigh-dose d-cycloserineAlcohol levelsReceptor functionPlacebo 4 hoursDouble-blind conditionsNMDA receptor functionNMDA glutamate receptorsMild sedative effectDoses of ethanolGlutamate receptor functionBreath alcohol levelsHuman subjectsVerbal fluencyGlycineB siteGroups of subjectsEthanol antagonismCombination of ethanolSedative effectsNMDA receptorsClinical significanceGlutamate receptors123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase
Cosgrove KP, Mitsis EM, Bois F, Frohlich E, Tamagnan GD, Krantzler E, Perry E, Maciejewski PK, Epperson CN, Allen S, O'Malley S, Mazure CM, Seibyl JP, van Dyck CH, Staley JK. 123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase. Journal Of Nuclear Medicine 2007, 48: 1633-1640. PMID: 17873128, DOI: 10.2967/jnumed.107.042317.Peer-Reviewed Original ResearchConceptsRegional brain activityMenstrual cycleNAChR availabilityWomen nonsmokersMenstrual phaseRadiotracer metabolismNicotinic acetylcholine receptor systemSex differencesBrain activityEffects of sexNicotinic acetylcholine receptor availabilitySmoking cessation treatmentMid-luteal phaseAcetylcholine receptor systemPlasma protein bindingTobacco smokingCessation treatmentHealthy menRegional brainHormone levelsPlasma measuresTreatment responseOutcome measuresSPECT scansNonsmokersPsychiatric safety of ketamine in psychopharmacology research
Perry EB, Cramer JA, Cho HS, Petrakis IL, Karper LP, Genovese A, O’Donnell E, Krystal JH, D’Souza D. Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacology 2007, 192: 253-260. PMID: 17458544, DOI: 10.1007/s00213-007-0706-2.Peer-Reviewed Original ResearchConceptsSubanesthetic dosesHealthy human subjectsKetamine administrationClinical research programHuman subjectsTest sessionsPsychotic spectrum disordersPsychiatric safetyResidual sequelaePlacebo infusionIntravenous infusionKetamine effectsPsychopharmacology studiesResultsFour hundredAdverse reactionsObjectiveTo reportHealthy subjectsStudy participationClinical investigationHealthy humansSide effectsKetamineInfusionDosesAdministration
2006
Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia
D'Souza DC, Gil RB, Madonick S, Perry EB, Forselius-Bielen K, Braley G, Donahue L, Tellioglu T, Zimolo Z, Gueorguieva R, Krystal JH. Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia. Neuropsychopharmacology 2006, 31: 2767-2775. PMID: 16985503, DOI: 10.1038/sj.npp.1301207.Peer-Reviewed Original ResearchConceptsEffects of alcoholHealthy subjectsBlood alcohol levelsPositive psychotic symptomsSmall transient increaseSelf-medication hypothesisPerceptual alterationsAlcohol administrationMotor functionAlcohol dosesElevated riskPsychotic symptomsLifetime exposureSchizophrenia patientsSchizophrenia symptomsEuphoric effectsNegative symptomsAlcohol levelsAlcohol useStimulatory effectSubjective effectsTransient increaseSchizophreniaStimulatory responseAlcohol responsesHuman Tobacco Smokers in Early Abstinence Have Higher Levels of β2* Nicotinic Acetylcholine Receptors than Nonsmokers
Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, Dubin JA, Estok K, Brenner E, Baldwin RM, Tamagnan GD, Seibyl JP, Jatlow P, Picciotto MR, London ED, O'Malley S, van Dyck CH. Human Tobacco Smokers in Early Abstinence Have Higher Levels of β2* Nicotinic Acetylcholine Receptors than Nonsmokers. Journal Of Neuroscience 2006, 26: 8707-8714. PMID: 16928859, PMCID: PMC6674379, DOI: 10.1523/jneurosci.0546-06.2006.Peer-Reviewed Original ResearchConceptsNAChR availabilityNicotinic acetylcholine receptorsEarly abstinenceAbstinent smokersHuman smokersAcetylcholine receptorsExpired carbon monoxide levelsAbility of smokersHuman tobacco smokersProperties of nicotineSingle photon emissionIA-85380Agonist radiotracerUrinary cotinineTobacco smokingTobacco smokersCerebral cortexLast cigaretteNicotine withdrawalWithdrawal symptomsPrevalent subtypeTobacco smokeAddictive chemicalNicotine dependenceSmokersGreater vulnerability to the amnestic effects of ketamine in males
Morgan CJ, Perry EB, Cho HS, Krystal JH, D’Souza D. Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology 2006, 187: 405-414. PMID: 16896964, DOI: 10.1007/s00213-006-0409-0.Peer-Reviewed Original ResearchConceptsAmnestic effectsProcessing of wordsGeneral cognitive functioningGreater performance decrementsGreater subjective senseGender differencesObjectivesThe current studyGreater vulnerabilityCognitive measuresCognitive differencesCognitive functioningPerceptual alterationsPerformance decrementsNMDA-R functionAttention dataMemory impairmentSubjective senseNegative symptomsCurrent studyFunctioningHVLTKetamine studiesAnxietyMemoryKetamine administrationPotentiation of Low Dose Ketamine Effects by Naltrexone: Potential Implications for the Pharmacotherapy of Alcoholism
Krystal JH, Madonick S, Perry E, Gueorguieva R, Brush L, Wray Y, Belger A, D'Souza DC. Potentiation of Low Dose Ketamine Effects by Naltrexone: Potential Implications for the Pharmacotherapy of Alcoholism. Neuropsychopharmacology 2006, 31: 1793-1800. PMID: 16395307, DOI: 10.1038/sj.npp.1300994.Peer-Reviewed Original ResearchConceptsNMDA glutamate receptorsNMDA receptor antagonismKetamine doseReceptor antagonismGlutamate receptorsKetamine effectsProtective effectPlacebo-controlled human laboratory studyOpiate receptor antagonismEfficacy of naltrexoneDose-related fashionNMDA receptor antagonist effectsReceptor antagonist effectsTotal PANSS scoreHuman laboratory studiesPharmacotherapy of alcoholismTreatment of alcoholismHealthy human subjectsHigher ketamine doseNegative Syndrome ScaleLower ketamine doseSignificant behavioral effectsSubanesthetic dosePANSS scoresEthanol drink