2023
Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia
Surti T, Ranganathan M, Johannesen J, Gueorguieva R, Deaso E, Kenney J, Krystal J, D'Souza D. Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia. Schizophrenia Research 2023, 256: 36-43. PMID: 37141764, PMCID: PMC10257994, DOI: 10.1016/j.schres.2023.04.010.Peer-Reviewed Original ResearchConceptsGlycine transporter 1Cytochrome P450 2D6 extensive metabolizersGlyT1 inhibitorsWeeks of washoutWeeks of CTMedication adherenceReceptor hypofunctionImpaired neuroplasticityPharmacodynamic variabilityNMDAR functionExtensive metabolizersTreatment periodPsychotic symptomsStable outpatientsCognitive impairmentGlyT1 occupancyTransporter 1CTNeuroplasticityCognitive training strategiesSchizophreniaComputerized CTCognitive performanceAugmentation studiesGreater improvement
2018
The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial
Boggs DL, Surti T, Gupta A, Gupta S, Niciu M, Pittman B, Schnakenberg Martin AM, Thurnauer H, Davies A, D’Souza D, Ranganathan M. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology 2018, 235: 1923-1932. PMID: 29619533, DOI: 10.1007/s00213-018-4885-9.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAffectAntipsychotic AgentsCannabidiolChronic DiseaseCognitionCognitive DysfunctionDouble-Blind MethodFemaleFollow-Up StudiesHumansMaleMental Status and Dementia TestsMiddle AgedOutpatientsPsychiatric Status Rating ScalesSchizophreniaSchizophrenic PsychologyTreatment OutcomeConceptsMATRICS Consensus Cognitive BatterySide effectsChronic schizophreniaAntipsychotic-treated patientsMovement side effectsFixed-dose studyPlacebo-treated subjectsWeeks of treatmentPANSS total scoreEffects of cannabidiolWorsening of moodNegative Syndrome ScaleAntipsychotic-treated outpatients× time effect× time interactionMCCB composite scoreOral cannabidiolCBD groupClinical trialsParallel groupPANSS scoresMethodsThis studyPsychotic symptomsConsensus Cognitive BatterySyndrome Scale17.2 EFFICACY OF CANNABIDIOL IN THE TREATMENT OF EARLY PSYCHOSIS.
Ranganathan M, D’Souza D, Cortes-Briones J, Skosnik P. 17.2 EFFICACY OF CANNABIDIOL IN THE TREATMENT OF EARLY PSYCHOSIS. Schizophrenia Bulletin 2018, 44: s27-s27. PMCID: PMC5887318, DOI: 10.1093/schbul/sby014.066.Peer-Reviewed Original ResearchEffects of cannabidiolEarly psychosisTreatment periodPsychotic symptomsFavorable side effect profileCritical treatment periodEfficacy of cannabidiolMedication side effectsSide effect profileAnti-psychotic effectsPhase of illnessWeeks of washoutTolerable medicationsCrossover studyEffect profileAntipsychotic medicationUntreated psychosisTraditional antipsychoticsEndocannabinoid systemMetabolic parametersPsychotic illnessElectrophysiological biomarkersSide effectsTreatment engagementPotential efficacy
2010
Probing GABA Receptor Function in Schizophrenia with Iomazenil
Ahn K, Gil R, Seibyl J, Sewell RA, D'Souza DC. Probing GABA Receptor Function in Schizophrenia with Iomazenil. Neuropsychopharmacology 2010, 36: 677-683. PMID: 21068719, PMCID: PMC3055690, DOI: 10.1038/npp.2010.198.Peer-Reviewed Original ResearchConceptsSchizophrenia patientsHealthy controlsGABA deficitHealthy subjectsBrief Psychiatric Rating ScaleGABA-deficit hypothesisPlacebo-controlled studyChronic schizophrenia patientsPathophysiology of schizophreniaPsychiatric Rating ScalePartial inverse agonistDissociative Symptoms ScaleGABA receptor functionPerceptual alterationsPsychotomimetic effectsPsychotic symptomsIomazenilBenzodiazepine receptorsPatientsSymptom ScalePharmacological inductionReceptor functionInverse agonistRating ScaleBrain imaging
2009
Cannabis and psychosis/schizophrenia: human studies
D’Souza D, Sewell RA, Ranganathan M. Cannabis and psychosis/schizophrenia: human studies. European Archives Of Psychiatry And Clinical Neuroscience 2009, 259: 413-431. PMID: 19609589, PMCID: PMC2864503, DOI: 10.1007/s00406-009-0024-2.Peer-Reviewed Original ResearchConceptsPsychotic disordersRole of cannabinoidsPsychosis/schizophreniaTransient psychotic symptomsComponent causesCannabinoid receptor functionCauses of schizophreniaWarrants further studyDuration of exposureCannabinoid exposureTrigger relapsePsychotic illnessPsychotic symptomsGeneral populationCognitive symptomsHealthy individualsHuman studiesReceptor functionCannabis useNeurodevelopmental processesCannabinoidsFirst exposureSymptomsDisordersGenetic factorsCannabinoids and psychosis
Sewell RA, Ranganathan M, D'Souza DC. Cannabinoids and psychosis. International Review Of Psychiatry 2009, 21: 152-162. PMID: 19367509, DOI: 10.1080/09540260902782802.Peer-Reviewed Original ResearchConceptsGeneral populationPsychotic disordersTrigger relapseCannabis usersCognitive symptomsCross-sectional studyIndividual vulnerabilityCannabis useCannabinoid receptor functionLongitudinal studyCase seriesPsychotic illnessPsychotic symptomsCannabisHealthy individualsSchizophreniaPharmacological studiesReceptor functionAutobiographical accountsPsychosisEarly exposureSymptomsTwo-fold increaseConsiderable evidenceComponent causes
2007
Cannabinoids and Psychosis
D'Souza DC. Cannabinoids and Psychosis. International Review Of Neurobiology 2007, 78: 289-326. PMID: 17349865, DOI: 10.1016/s0074-7742(06)78010-2.Peer-Reviewed Original ResearchConceptsReceptor dysfunctionPsychotic disordersTransient psychotic symptomsRecent epidemiological studiesComponent causesRates of cannabisRates of schizophreniaCauses of schizophreniaWarrants further studyAcute psychosisLung cancerCannabis exposureCannabinoid functionHigh riskPsychotic symptomsEpidemiological studiesPeriod of intoxicationPsychosisAvailable evidenceSchizophreniaCannabinoidsGenetic riskBiological plausibilityFurther studiesDysfunction
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 responses
2004
Cannabinoid ‘model’ psychosis, dopamine–cannabinoid interactions and implications for schizophrenia
D'souza D, Cho H, Perry E, Krystal J. Cannabinoid ‘model’ psychosis, dopamine–cannabinoid interactions and implications for schizophrenia. 2004, 142-165. DOI: 10.1017/cbo9780511543630.012.Peer-Reviewed Original ResearchReceptor dysfunctionCannabinoid compoundsCannabis consumptionPathophysiology of psychosisPathophysiology of schizophreniaRecent pharmacological studiesPrincipal psychoactive constituentEffects of exposurePostmortem studiesNormal controlsPsychotic symptomsPsychotic disordersPharmacological studiesPsychosisPsychoactive constituentPathophysiologyΔ9-tetrahydrocannabinolSchizophreniaCannabisDysfunctionAssociationPossible mechanismPatientsSymptomsPharmacological
1999
No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia
Abi-Dargham A, Laruelle M, Krystal J, D'Souza C, Zoghbi S, Baldwin R, Seibyl J, Mawlawi O, de Erasquin G, Charney D, Innis R. No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia. Neuropsychopharmacology 1999, 20: 650-661. PMID: 10327433, DOI: 10.1016/s0893-133x(98)00107-9.Peer-Reviewed Original ResearchConceptsReceptor densitySchizophrenic patientsVivo benzodiazepine receptor bindingBDZ receptor densityMale schizophrenic patientsBenzodiazepine receptor densityPathophysiology of schizophreniaBenzodiazepine receptor bindingSingle photon emissionRegional distribution volumesPrevious postmortemGABA transmissionBDZ antagonistBDZ receptorsReceptor expressionNeurotransmitter systemsHealthy volunteersPsychotic symptomsBrain regionsDistribution volumeReceptor bindingSchizophreniaVivo studiesPatientsPossible alterations
1996
Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.
Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 9235-9240. PMID: 8799184, PMCID: PMC38625, DOI: 10.1073/pnas.93.17.9235.Peer-Reviewed Original ResearchConceptsAmphetamine-induced dopamine releaseDopamine releaseDopaminergic transmissionPsychotic symptomsSchizophrenic groupDopamine D2 receptor availabilityAmphetamine-induced decreaseAmphetamine-induced reductionD2 receptor availabilityD2 receptor radiotracerPositive psychotic symptomsSingle photon emissionExaggerated stimulationAbnormal responsivenessDopaminergic neuronsHealthy controlsReceptor radiotracerSchizophrenic patientsDopamine hypothesisDopamine functionReceptor availabilityAmphetamine effectsControl groupSchizophrenic subjectsSchizophrenia