2023
Dysregulation of the endogenous cannabinoid system following opioid exposure
Mohammad Aghaei A, Saali A, Canas M, Weleff J, D'Souza D, Angarita G, Bassir Nia A. Dysregulation of the endogenous cannabinoid system following opioid exposure. Psychiatry Research 2023, 330: 115586. PMID: 37931479, PMCID: PMC10842415, DOI: 10.1016/j.psychres.2023.115586.Peer-Reviewed Original ResearchConceptsEndocannabinoid systemECS componentsBrain regionsNovel neurobiological targetsTreatment of OUDEndogenous opioid systemOpioid-related deathsEndogenous cannabinoid systemSpecific brain regionsECS dysregulationOpioid exposureOUD treatmentOpioid systemCannabinoid systemNeurobiological targetsNew medicationsPreclinical literatureCannabinoid receptorsEndogenous ligandTherapeutic potentialStudy typePresent potential targetsExposure protocolOpioidsPreclinical research
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
In vivo evidence of lower synaptic vesicle density in schizophrenia
Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, Hillmer AT, Esterlis I, Huang Y, Nabulsi N, Carson RE, D’Souza D. In vivo evidence of lower synaptic vesicle density in schizophrenia. Molecular Psychiatry 2021, 26: 7690-7698. PMID: 34135473, DOI: 10.1038/s41380-021-01184-0.Peer-Reviewed Original ResearchConceptsSynaptic vesicle densityHealthy controlsVesicle densityHigh-resolution research tomographySynaptic densitySCZ patientsVivo measuresNovel positron emission tomography (PET) ligandGender-matched healthy controlsCumulative antipsychotic exposurePositron emission tomography (PET) ligandSynaptic spine densityPsychosis symptom severityGray matter volumeJ bindingAntipsychotic exposureSpine densityDisease progressionFrontal cortexOccipital cortexTomography ligandTemporal cortexAnterior cingulateVivo findingsParietal cortexIdentifying 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
Preliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder
D’Souza D, Radhakrishnan R, Naganawa M, Ganesh S, Nabulsi N, Najafzadeh S, Ropchan J, Ranganathan M, Cortes-Briones J, Huang Y, Carson RE, Skosnik P. Preliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder. Molecular Psychiatry 2020, 26: 3192-3200. PMID: 32973170, DOI: 10.1038/s41380-020-00891-4.Peer-Reviewed Original ResearchConceptsHippocampal synaptic densityCannabis use disorderHealthy controlsSynaptic densityPositron emission tomographyUse disordersDSM-5 cannabis use disorderVivo evidenceAdministration of cannabinoidsHippocampal synaptic integrityVerbal memory taskSynaptic vesicle glycoprotein 2AHuman cannabis usersEffects of cannabisWarrants further studyPlasma input functionMemory taskCentrum semiovaleAdult rodentsOne-tissue compartment modelSynaptic integrityHippocampal functionCannabis misuseArterial samplingEmission tomography
2019
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
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 effortsGrey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence
Orr C, Spechler P, Cao Z, Albaugh M, Chaarani B, Mackey S, D'Souza D, Allgaier N, Banaschewski T, Bokde ALW, Bromberg U, Büchel C, Quinlan E, Conrod P, Desrivières S, Flor H, Frouin V, Gowland P, Heinz A, Ittermann B, Martinot JL, Martinot MP, Nees F, Orfanos D, Paus T, Poustka L, Millenet S, Fröhner JH, Radhakrishnan R, Smolka MN, Walter H, Whelan R, Schumann G, Potter A, Garavan H. Grey Matter Volume Differences Associated with Extremely Low Levels of Cannabis Use in Adolescence. Journal Of Neuroscience 2019, 39: 1817-1827. PMID: 30643026, PMCID: PMC6407302, DOI: 10.1523/jneurosci.3375-17.2018.Peer-Reviewed Original ResearchConceptsGray matter volumeCannabis useCannabis usersPerceptual Reasoning IndexGreater gray matter volumeMedial temporal lobeBilateral posterior cingulateGeneralized anxiety symptomsBilateral medial temporal lobesInitiation of cannabisRates of cannabisLong-term neurocognitive effectsGray matter volume differencesCognitive effectsHuman adolescentsNeurocognitive effectsAnxiety symptomsVoxel-based morphometryLingual gyrusPosterior cingulateRecreational cannabis useAdolescent periodTemporal regionsHeavy patternNeural maturation
2018
The Psychiatric Consequences of Cannabinoids
De Aquino JP, Sherif M, Radhakrishnan R, Cahill JD, Ranganathan M, D'Souza D. The Psychiatric Consequences of Cannabinoids. Clinical Therapeutics 2018, 40: 1448-1456. PMID: 29678279, DOI: 10.1016/j.clinthera.2018.03.013.Peer-Reviewed Original ResearchConceptsPsychiatric effectsPsychiatric disordersPre-existing psychiatric disordersCannabis useLong-term brain changesRates of cannabisNegative psychiatric outcomesNegative psychiatric effectsDose-dependent effectPublic mental healthCannabinoid exposureWithdrawal syndromeCannabis exposureAcute effectsBrain changesMood disordersPsychiatric outcomesGeneral populationPsychomotor functionHealthy individualsMedical cannabisPsychiatric consequencesChronic exposureSignificant impairmentMental healthCannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans
Skosnik PD, Hajós M, Cortes-Briones JA, Edwards CR, Pittman BP, Hoffmann WE, Sewell AR, D'Souza DC, Ranganathan M. Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans. Neuropharmacology 2018, 135: 412-423. PMID: 29604295, PMCID: PMC6091633, DOI: 10.1016/j.neuropharm.2018.03.036.Peer-Reviewed Original ResearchConceptsLocal field potentialsSensory gatingCP 55940AM 251Dual-click paradigmNeural oscillationsCannabinoid receptor 1P50 gating ratioGating ratioCannabinoid administrationCB1R agonistEndocannabinoid systemOutcome measuresTranslational studiesReceptor 1Brain regionsAnimal dataCannabis useRatsCannabidiolPlaceboTHC conditionsField potentialsTest dayHuman subjectsDose-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
Targeted neural network interventions for auditory hallucinations: Can TMS inform DBS?
Taylor JJ, Krystal JH, D'Souza DC, Gerrard JL, Corlett PR. Targeted neural network interventions for auditory hallucinations: Can TMS inform DBS? Schizophrenia Research 2017, 195: 455-462. PMID: 28969932, PMCID: PMC8141945, DOI: 10.1016/j.schres.2017.09.020.Peer-Reviewed Original ResearchConceptsDeep brain stimulationTranscranial magnetic stimulationAuditory hallucinationsBrain stimulationCombination of TMSTreatment-refractory schizophreniaAberrant neural networksRelevant neural networksNon-invasive formNeuromodulatory interventionsMagnetic stimulationPsychiatric disordersSymptom clusteringTherapeutic interventionsClinical decisionInvasive formNeurophysiological dataCausal evidencePsychiatric constructsStimulationNetwork modulationInterventionNeural networkSafety concernsInvestigational probes
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 doses
2015
Medical Marijuana: Is the Cart Before the Horse?
D'Souza DC, Ranganathan M. Medical Marijuana: Is the Cart Before the Horse? JAMA 2015, 313: 2431-2432. PMID: 26103026, DOI: 10.1001/jama.2015.6407.Peer-Reviewed Original Research
2014
Going up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia.
Boggs DL, Carlson J, Cortes-Briones J, Krystal JH, D'Souza DC. Going up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia. Current Pharmaceutical Design 2014, 20: 5077-92. PMID: 24345265, PMCID: PMC4442779, DOI: 10.2174/1381612819666131216121019.Peer-Reviewed Original ResearchConceptsCognitive impairmentStandardized cognitive test batteryCognitive test batteryInformation processing impairmentsNicotinic medicationsProcessing impairmentsCore deficitAttentional deficitsTest batteryCognitive deficitsProximal measuresBrain functionCognitionSchizophreniaDeficitsImpairmentNumber of medicationsNicotinic acetylcholine receptorsCertain symptomsConsistent improvementClinical evidenceTreatment strategiesClinical studiesNicotinic receptorsClinical utility
2013
In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia
Esterlis I, Ranganathan M, Bois F, Pittman B, Picciotto MR, Shearer L, Anticevic A, Carlson J, Niciu MJ, Cosgrove KP, D’Souza D. In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia. Biological Psychiatry 2013, 76: 495-502. PMID: 24360979, PMCID: PMC4019710, DOI: 10.1016/j.biopsych.2013.11.001.Peer-Reviewed Original ResearchConceptsLower β2Negative symptomsCortical regionsLower receptor availabilitySelf-medicate symptomsComparison groupLower negative symptomsHigh β2Executive controlExecutive functionNicotine cravingSex-matched comparison subjectsMood assessmentBrain regionsWorse performanceComparison subjectsDiagnosis interactionLimited brain regionsNicotinic acetylcholine receptorsSchizophreniaSingle photon emissionNAChR availabilityActive smokingTobacco smokingPoor outcomeEffect of a Nicotine Vaccine on Nicotine Binding to β2*-Nicotinic Acetylcholine Receptors In Vivo in Human Tobacco Smokers
Esterlis I, Hannestad JO, Perkins E, Bois F, D’Souza D, Tyndale RF, Seibyl JP, Hatsukami DM, Cosgrove KP, O’Malley S. Effect of a Nicotine Vaccine on Nicotine Binding to β2*-Nicotinic Acetylcholine Receptors In Vivo in Human Tobacco Smokers. American Journal Of Psychiatry 2013, 170: 399-407. PMID: 23429725, PMCID: PMC3738000, DOI: 10.1176/appi.ajp.2012.12060793.Peer-Reviewed Original ResearchConceptsNicotine vaccineNicotinic acetylcholine receptorsNicotine bindingAmount of nicotineAcetylcholine receptorsHuman tobacco smokersSingle photon emissionTobacco smokersNicotine promotesScan daySmokers' brainsIntravenous administrationEmission scansNicotine dependenceSPECT scansSubcortical regionsNAChRsNicotineImmunizationVT/VaccineCigarettesBrainCessation difficultiesSmokers
2008
Blunted 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
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
Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects
Neumeister A, Carson R, Henry S, Planeta-Wilson B, Binneman B, Maguire RP, Luckenbaugh DA, D'Souza C, Krystal JH, Frost JJ. Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects. Journal Of Clinical Psychopharmacology 2006, 26: 595-599. PMID: 17110816, DOI: 10.1097/01.jcp.0000245558.14284.aa.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntipsychotic AgentsBehaviorBrainBrain MappingCluster AnalysisCross-Over StudiesDouble-Blind MethodFemaleFluorodeoxyglucose F18GlycineHumansInfusions, IntravenousMagnetic Resonance ImagingMaleNeuropsychological TestsPositron-Emission TomographyRadiopharmaceuticalsReference ValuesSerineConceptsN-methyl-D-aspartate receptor functionReceptor functionRegional cerebral metabolic rateAdministration of glycineCerebral metabolic effectsMagnetic resonance imaging studyPositron emission tomography studyHealthy control subjectsNMDA receptor functionCerebral metabolic rateEmission tomography studiesTest dayHealthy human subjectsResonance imaging studySignificant reductionPositron emission tomographyDorsolateral prefrontal cortexIntravenous glycinePlacebo infusionCerebral metabolismPatient populationControl subjectsGlycine administrationGlycine infusionIntravenous administrationEnhanced 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