2024
Amygdala Cannabinoid 1 Receptor, Pain Response, and Emotional Numbing in Trauma-Exposed Individuals
Korem N, Hillmer A, D’Souza D, Nia A, Levy I, Pietrzak R, Harpaz-Rotem I. Amygdala Cannabinoid 1 Receptor, Pain Response, and Emotional Numbing in Trauma-Exposed Individuals. JAMA Network Open 2024, 7: e2432387. PMID: 39250156, PMCID: PMC11385051, DOI: 10.1001/jamanetworkopen.2024.32387.Peer-Reviewed Original Research
2023
Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles
Ganesh S, Lam T, Garcia-Milian R, D'Souza D, Nairn A, Elgert K, Eitan E, Ranganathan M. Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles. The World Journal Of Biological Psychiatry 2023, 24: 603-613. PMID: 36994633, PMCID: PMC10471733, DOI: 10.1080/15622975.2023.2197039.Peer-Reviewed Original ResearchMeSH KeywordsExtracellular VesiclesHumansMarijuana AbusePilot ProjectsProteomicsSubstance-Related DisordersYoung AdultConceptsNeuron-derived extracellular vesiclesLabel-free quantification mass spectrometryProteomic studiesCannabis use disorderExtracellular vesiclesMass spectrometry proteomic analysisDifferential proteomic profilesAdapter proteinProteomic analysisPost-synaptic densityPeripheral signatureMolecular basisProteomic profilesProteinMarkers of neuropathologyBrain tissue samplesSynaptic pathologyVesiclesSynaptic integrityImmunoaffinity methodUse disordersFunctional integrityImportant insightsNeuropathologyPilot study
2022
Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET
Radhakrishnan R, Worhunsky PD, Zheng MQ, Najafzadeh S, Gallezot JD, Planeta B, Henry S, Nabulsi N, Ranganathan M, Skosnik PD, Pittman B, Cyril D'Souza D, Carson RE, Huang Y, Potenza MN, Matuskey D. Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET. NeuroImage 2022, 264: 119674. PMID: 36243269, DOI: 10.1016/j.neuroimage.2022.119674.Peer-Reviewed Original Research
2021
Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis
Fang XT, Toyonaga T, Hillmer AT, Matuskey D, Holmes SE, Radhakrishnan R, Mecca AP, van Dyck CH, D’Souza D, Esterlis I, Worhunsky PD, Carson RE. Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis. NeuroImage 2021, 237: 118167. PMID: 34000404, PMCID: PMC8452380, DOI: 10.1016/j.neuroimage.2021.118167.Peer-Reviewed Original ResearchConceptsSynaptic densityResting-state functional magnetic resonance imagingSynaptic vesicle protein 2ALevel-dependent signal fluctuationsBrain networksFunctional magnetic resonance imagingMagnetic resonance imagingAge-related changesHealthy controlsResonance imagingRs-fMRIEffects of sexProtein 2AMultiple comparisonsHuman brainAgePotential utilitySexFirst evidenceCovariance patterns
2020
Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin
Schindler EAD, Sewell RA, Gottschalk CH, Luddy C, Flynn LT, Lindsey H, Pittman BP, Cozzi NV, D'Souza D. Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin. Neurotherapeutics 2020, 18: 534-543. PMID: 33184743, PMCID: PMC8116458, DOI: 10.1007/s13311-020-00962-y.Peer-Reviewed Original ResearchConceptsTherapeutic effectAdverse eventsSingle administrationPsychotropic effectsWeekly migraine daysSerious adverse eventsCross-over studyEffects of psilocybinOral placeboMigraine daysMigraine frequencyClinical effectsControlled StudyHeadache disordersMigraine headacheHeadache diaryDrug effectsDrug AdministrationNeuropsychiatric conditionsMigraineFinal analysisStudy proceduresReceptor ligandsWeeksAdministrationSingle-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Hu Y, Ranganathan M, Shu C, Liang X, Ganesh S, Osafo-Addo A, Yan C, Zhang X, Aouizerat BE, Krystal JH, D’Souza D, Xu K. Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Scientific Reports 2020, 10: 3450. PMID: 32103029, PMCID: PMC7044203, DOI: 10.1038/s41598-020-59827-1.Peer-Reviewed Original ResearchConceptsSpecific genesCell type-specific genesGene expressionSingle-cell transcriptomic profilingCell typesGene expression correlationsAlters gene expressionTranscriptome mappingTranscriptomic profilingExpression correlationEnrichment analysisCommon genesImportant medical implicationsSignificant genesGenesMajor immune cell typesCell proliferationImmune cell typesImmune responseCell toxicityMedical implicationsCellsImportant insightsExpressionHuman immune cells
2019
In vivo 5-HT6 and 5-HT2A receptor availability in antipsychotic treated schizophrenia patients vs. unmedicated healthy humans measured with [11C]GSK215083 PET
Radhakrishnan R, Matuskey D, Nabulsi N, Gaiser E, Gallezot JD, Henry S, Planeta B, Lin SF, Ropchan J, Huang Y, Carson RE, D'Souza DC. In vivo 5-HT6 and 5-HT2A receptor availability in antipsychotic treated schizophrenia patients vs. unmedicated healthy humans measured with [11C]GSK215083 PET. Psychiatry Research Neuroimaging 2019, 295: 111007. PMID: 31760336, DOI: 10.1016/j.pscychresns.2019.111007.Peer-Reviewed Original ResearchConceptsHealthy male controlsPositron emission tomographyMultilinear analysis 1Antipsychotic treatmentLower BPFrontal cortexReceptor availabilityAge-matched healthy male controlsDifferent second-generation antipsychoticsSteady-state troughPeak serum levelsSecond-generation antipsychoticsPotential therapeutic targetMale patientsSerum levelsHealthy humansTherapeutic targetSchizophrenia patientsTime-activity curvesMale controlsCognitive impairmentEmission tomographyVentral striatumPatientsSchizophreniaCharacterizing psychosis-relevant phenomena and cognitive function in a unique population with isolated, chronic and very heavy cannabis exposure
D'Souza DC, Ganesh S, Cortes-Briones J, Campbell MH, Emmanuel MK. Characterizing psychosis-relevant phenomena and cognitive function in a unique population with isolated, chronic and very heavy cannabis exposure. Psychological Medicine 2019, 50: 2452-2459. PMID: 31615592, DOI: 10.1017/s0033291719002721.Peer-Reviewed Original ResearchConceptsSchizotypal Personality QuestionnaireCognitive performanceCannabis exposureTests of attentionComputerized cognitive batteryVisuo-spatial processingHigher SPQ scoresSubstance use/misuseWorse cognitive performanceHeavy cannabis exposureLarge effect sizesUse/misuseCognitive flexibilityVerbal memoryCognitive batteryCognitive functioningPsychomotor speedSPQ scoresCognitive functionCognitive deficitsCannabis usersPersonality QuestionnaireCannabis useUse of cannabisEarly cannabisHighs and lows of cannabinoid-dopamine interactions: effects of genetic variability and pharmacological modulation of catechol-O-methyl transferase on the acute response to delta-9-tetrahydrocannabinol in humans
Ranganathan M, De Aquino JP, Cortes-Briones JA, Radhakrishnan R, Pittman B, Bhakta S, D’Souza D. Highs and lows of cannabinoid-dopamine interactions: effects of genetic variability and pharmacological modulation of catechol-O-methyl transferase on the acute response to delta-9-tetrahydrocannabinol in humans. Psychopharmacology 2019, 236: 3209-3219. PMID: 31187152, DOI: 10.1007/s00213-019-05273-5.Peer-Reviewed Original ResearchConceptsCOMT rs4680 polymorphismMemory deficitsCOMT genotypeVal/Val individualsRs4680 polymorphismSubjective effectsTest dayCatechol-O-methyl transferase (COMT) enzymePsychotomimetic effectsCognitive effectsCognitive dataCannabinoid-dopamine interactionsAcute responseHuman brainIntravenous THCPlacebo-controlled studyRole of dopaminergicCatechol-O-methyl transferaseDopaminergic signalingAcute pharmacological inhibitionDeficitsCannabinoid effectsDopaminergic toneHealthy subjectsDrug development effortsEffects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis
Gupta S, De Aquino JP, D’Souza D, Ranganathan M. Effects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis. Psychopharmacology 2019, 236: 2635-2640. PMID: 30919005, PMCID: PMC6697616, DOI: 10.1007/s00213-019-05235-x.Peer-Reviewed Original ResearchConceptsDissociative Symptoms ScalePANSS positive scalePsychotomimetic effectsHuman laboratory studiesRole of dopaminePsychosis-like effectsHaloperidol conditionNegative Syndrome ScalePANSS positive scoreDopaminergic antagonismPositive scalePlacebo conditionResponder analysisSyndrome ScaleSymptom ScaleDouble-blind studyEffects of haloperidolDopaminergic signalingOral haloperidolIndividualsOnly respondersPositive scoreIntravenous administrationHealthy individualsHaloperidol
2018
Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial
D'Souza DC, Cortes-Briones J, Creatura G, Bluez G, Thurnauer H, Deaso E, Bielen K, Surti T, Radhakrishnan R, Gupta A, Gupta S, Cahill J, Sherif MA, Makriyannis A, Morgan PT, Ranganathan M, Skosnik PD. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. The Lancet Psychiatry 2018, 6: 35-45. PMID: 30528676, DOI: 10.1016/s2215-0366(18)30427-9.Peer-Reviewed Original ResearchConceptsPF-04457845Cannabis withdrawal symptomsFatty acid amide hydrolaseCannabis withdrawalPlacebo groupAdverse eventsCannabis useWithdrawal symptomsFatty acid amide hydrolase inhibitorSerious adverse eventsPhase 2a trialWeeks of treatmentTreatment of cannabisCannabis use disorderSelf-reported cannabis useDSM-IV criteriaTreatment-related differencesTHC-COOH concentrationsAnandamide concentrationsTreat populationPrimary endpointPill countHospital admissionNovel FAAH inhibitorsSelf-reported cannabisHerpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study
Breier A, Buchanan RW, D'Souza D, Nuechterlein K, Marder S, Dunn W, Preskorn S, Macaluso M, Wurfel B, Maguire G, Kakar R, Highum D, Hoffmeyer D, Coskinas E, Litman R, Vohs JL, Radnovich A, Francis MM, Metzler E, Visco A, Mehdiyoun N, Yang Z, Zhang Y, Yolken RH, Dickerson FB. Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study. Schizophrenia Research 2018, 206: 291-299. PMID: 30478008, DOI: 10.1016/j.schres.2018.11.002.Peer-Reviewed Original ResearchConceptsHSV-1Double-blind efficacy trialHerpes simplex virus 1 (HSV-1) infectionEarly phase schizophreniaSimplex virus 1 infectionVirus-1 infectionPathophysiology of schizophreniaPrimary endpointValacyclovir treatmentNegative subjectsRecent trialsVISTA studyEfficacy trialsLetter-Number Sequencing TestNegative groupPositive groupSevere formHerpes virusPositive symptomsMore impairmentTreatment resultsUS sitesCognitive deficitsNon-activated stateSchizophreniaThe dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ9-THC) in humans
Boggs DL, Cortes-Briones JA, Surti T, Luddy C, Ranganathan M, Cahill JD, Sewell AR, D’Souza D, Skosnik PD. The dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ9-THC) in humans. Journal Of Psychopharmacology 2018, 32: 1308-1318. PMID: 30255720, DOI: 10.1177/0269881118799953.Peer-Reviewed Original ResearchConceptsFine motor controlPsychomotor effectsMotor functionPsychomotor functionCannabinoid receptor type 1Motor controlGross motor functionDose-related effectsObserved dose-dependent increaseDose-dependent increaseDose-dependent deficitsMotor timingReceptor type 1Gross motor performancePotential neural mechanismsCambridge Neuropsychological TestMotor deficitsBasal gangliaBlood levelsMotor impairmentDrug conditionsPartial agonistGrooved Pegboard taskSustained attentionType 1Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET
Radhakrishnan R, Nabulsi N, Gaiser E, Gallezot JD, Henry S, Planeta B, Lin SF, Ropchan J, Williams W, Morris E, D'Souza DC, Huang Y, Carson RE, Matuskey D. Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET. Journal Of Nuclear Medicine 2018, 59: 1445-1450. PMID: 29626125, PMCID: PMC6126437, DOI: 10.2967/jnumed.117.206516.Peer-Reviewed Original ResearchDose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects
D’Souza D, Carson RE, Driesen N, Johannesen J, Ranganathan M, Krystal JH, Ahn K, Bielen K, Carbuto M, Deaso E, D’Souza D, Ranganathan M, Naganawa M, Ranganathan M, D’Souza D, Nabulsi N, Zheng M, Lin S, Huang Y, Carson R, Driesen N, Ahn K, Morgan P, Suckow R, He G, McCarthy G, Krystal J, Johannesen J, Kenney J, Gelernter J, Gueorguieva R, Pittman B. Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects. Biological Psychiatry 2018, 84: 413-421. PMID: 29499855, PMCID: PMC6068006, DOI: 10.1016/j.biopsych.2017.12.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzabicyclo CompoundsBrainCognitive DysfunctionDose-Response Relationship, DrugDouble-Blind MethodFemaleGlycine Plasma Membrane Transport ProteinsHumansImidazolesKetamineLong-Term PotentiationMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedPositron-Emission TomographySchizophreniaYoung AdultConceptsHealthy control subjectsLong-term potentiationSchizophrenia patientsControl subjectsCognitive impairmentClinical trialsGlyT1 occupancyN-methyl-D-aspartate receptor functionGlycine transporter-1 inhibitorKetamine-induced disruptionKetamine-induced effectsFunctional magnetic resonance imagingMagnetic resonance imagingPositron emission tomographyMemory-related activationF-MKSubstudy 1Schizophrenia subjectsResonance imagingReceptor functionCortical regionsEmission tomographyTarget engagementPotentiationSchizophrenia
2017
Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia
Hamilton HK, D'Souza DC, Ford JM, Roach BJ, Kort NS, Ahn KH, Bhakta S, Ranganathan M, Mathalon DH. Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia. Schizophrenia Research 2017, 191: 87-94. PMID: 28711472, PMCID: PMC5745273, DOI: 10.1016/j.schres.2017.06.040.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptor agonistAcetylcholine receptor agonistReceptor agonistHealthy volunteersN-methyl-D-aspartate receptor antagonistPathophysiology of schizophreniaAuditory processing abnormalitiesProfile of effectsMMN amplitudeNicotine preventsNicotine administrationReceptor hypofunctionNMDAR hypofunctionNMDAR antagonistsReceptor antagonistMismatch negativity (MMN) event-related potential (ERP) componentPresent doseNicotinic agonistsSchizophrenia patientsCigarette useKetamineDeviant typesNeurophysiological effectsSecondary analysisMMN abnormalitiesTetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information
Ranganathan M, Radhakrishnan R, Addy PH, Schnakenberg-Martin AM, Williams AH, Carbuto M, Elander J, Pittman B, Sewell R, Skosnik PD, D'Souza DC. Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2017, 79: 176-183. PMID: 28642081, DOI: 10.1016/j.pnpbp.2017.06.019.Peer-Reviewed Original ResearchConceptsRey Auditory Verbal Learning TestVerbal informationInfluence of tetrahydrocannabinolVerbal Learning TestMemory-impairing effectsTotal immediate recallNon-verbal informationImpairs memory consolidationAdministration of tetrahydrocannabinolAcute memory impairmentPrincipal psychoactive constituentVerbal memoryImmediate recallIntravenous tetrahydrocannabinolLearning TestMemory consolidationComponent processesNeural synchronyMemory impairmentInformation processingUse of cannabisCannabis intoxicationRecallPsychoactive constituentEncoding
2016
Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO
Girgis RR, Slifstein M, D’Souza D, Lee Y, Periclou A, Ghahramani P, Laszlovszky I, Durgam S, Adham N, Nabulsi N, Huang Y, Carson RE, Kiss B, Kapás M, Abi-Dargham A, Rakhit A. Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO. Psychopharmacology 2016, 233: 3503-3512. PMID: 27525990, PMCID: PMC5035321, DOI: 10.1007/s00213-016-4382-y.Peer-Reviewed Original ResearchConceptsDopamine D3 receptorD2 receptorsD3 receptorsReceptor occupancyPartial agonistPositive symptomsD2 receptor partial agonistNegative symptomsPositron emission tomography scanDose-occupancy relationshipD2 receptor occupancyWeeks of dosingEmission tomography scanWeeks of treatmentExposure-response analysisReceptor partial agonistCerebrospinal fluid samplesDopamine D2 receptorsReward-related behaviorsD2 receptor ligandsTomography scanD2 antagonismPatientsDay 1Low dosesFeasibility and success of cell-phone assisted remote observation of medication adherence (CAROMA) in clinical trials
DeWorsop D, Creatura G, Bluez G, Thurnauer H, Forselius-Bielen K, Ranganathan M, Deaso E, Bhat JA, D’Souza D. Feasibility and success of cell-phone assisted remote observation of medication adherence (CAROMA) in clinical trials. Drug And Alcohol Dependence 2016, 163: 24-30. PMID: 27068252, DOI: 10.1016/j.drugalcdep.2016.02.045.Peer-Reviewed Original ResearchConceptsMedication adherenceClinical trialsStudy medicationMedication nonadherenceDrug levelsActive study medicationWeekly study visitsPlacebo-controlled trialPlasma drug levelsSubstance abuse disordersPill countStudy visitStudy completionFace visitsClinical careAbuse disordersMedicationsCannabis dependencePilot studyTrialsAdherenceVisitsNonadherenceWeekly faceHigh rate
2015
Reduced Brain Cannabinoid Receptor Availability in Schizophrenia
Ranganathan M, Cortes-Briones J, Radhakrishnan R, Thurnauer H, Planeta B, Skosnik P, Gao H, Labaree D, Neumeister A, Pittman B, Surti T, Huang Y, Carson RE, D’Souza D. Reduced Brain Cannabinoid Receptor Availability in Schizophrenia. Biological Psychiatry 2015, 79: 997-1005. PMID: 26432420, PMCID: PMC4884543, DOI: 10.1016/j.biopsych.2015.08.021.Peer-Reviewed Original ResearchConceptsHealthy control subjectsSCZ subjectsCB1R availabilityECB systemMale healthy control subjectsBody mass indexAge-matched male healthy control subjectsPathophysiology of schizophreniaPositron emission tomographyPosterior cingulate cortexPresence of abnormalitiesMass indexControl subjectsEndocannabinoid systemTobacco useReceptor availabilityCingulate cortexEmission tomography dataBrain regionsEmission tomographySelective radiotracerVivo measuresRegional volumesSchizophreniaPositron emission tomography data