2022
Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder
D’Souza D, Syed SA, Flynn LT, Safi-Aghdam H, Cozzi NV, Ranganathan M. Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. Neuropsychopharmacology 2022, 47: 1854-1862. PMID: 35660802, PMCID: PMC9372173, DOI: 10.1038/s41386-022-01344-y.Peer-Reviewed Original ResearchConceptsMajor depressive disorderHealthy controlsAntidepressant effectsDosing sessionsPsychotomimetic effectsDepressive disorderAbuse liabilityTreatment-resistant major depressive disorderDose-related safetyTreatment-resistant individualsMDD participantsPhase 1 studyHAMD-17 scoresTreatment of depressionFurther rigorous trialsMin of injectionExploratory pilot studyPsychedelic drugsAdverse eventsBlood pressureHAMD-17Cardiovascular functionRigorous trialsHealthy volunteersHeart rate
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 patternsAnalysis of circulating exosomes reveals a peripheral signature of astrocytic pathology in schizophrenia
Ranganathan M, Rahman M, Ganesh S, D’Souza D, Skosnik PD, Radhakrishnan R, Pathania S, Mohanakumar T. Analysis of circulating exosomes reveals a peripheral signature of astrocytic pathology in schizophrenia. The World Journal Of Biological Psychiatry 2021, 23: 33-45. PMID: 33821753, DOI: 10.1080/15622975.2021.1907720.Peer-Reviewed Original ResearchConceptsHealthy controlsSex-matched healthy controlsBlood-brain barrierNovel peripheral biomarkersPlasma-derived exosomesAstroglial pathologyWestern blot analysisPeripheral biomarkersSynaptophysin levelsBrain barrierPeripheral signatureAstrocytic pathologyGFAP concentrationsSchizophrenia patientsExosomal protein expressionNeuropsychiatric disordersNeurodegenerative disordersProtein immunopositivitySchizophreniaProtein expressionGroup differencesDisordersPatientsScarce dataConcentration of exosomes
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
2017
Opposing Effects of Cannabis Use on Electroencephalographic Measures of Auditory Repetition Suppression in Schizophrenia and Healthy Controls
Skosnik PD, D’Souza D. Opposing Effects of Cannabis Use on Electroencephalographic Measures of Auditory Repetition Suppression in Schizophrenia and Healthy Controls. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2017, 2: 209-211. PMID: 29528290, DOI: 10.1016/j.bpsc.2017.03.004.Peer-Reviewed Original Research
2016
Rapid Changes in Cannabinoid 1 Receptor Availability in Cannabis-Dependent Male Subjects After Abstinence From Cannabis
D’Souza D, Cortes-Briones JA, Ranganathan M, Thurnauer H, Creatura G, Surti T, Planeta B, Neumeister A, Pittman B, Normandin M, Kapinos M, Ropchan J, Huang Y, Carson RE, Skosnik PD. Rapid Changes in Cannabinoid 1 Receptor Availability in Cannabis-Dependent Male Subjects After Abstinence From Cannabis. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2016, 1: 60-67. PMID: 26858993, PMCID: PMC4742341, DOI: 10.1016/j.bpsc.2015.09.008.Peer-Reviewed Original Research
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
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 impairmentBlunted 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
1999
CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls: Prediction of Alcohol Cue‐Induced Craving?
Petrakis I, Trevisan L, D'Souza C, Gil R, Krasnicki S, Webb E, Heninger G, Cooney N, Krystal J. CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls: Prediction of Alcohol Cue‐Induced Craving? Alcohol Clinical And Experimental Research 1999, 23: 1336-1341. PMID: 10470976, DOI: 10.1111/j.1530-0277.1999.tb04355.x.Peer-Reviewed Original ResearchConceptsAlcohol-dependent patientsHealthy controlsEndorphin levelsCSF levelsMonoamine metabolitesCSF measuresHealthy subjectsNorepinephrine metabolite MHPGLower CSF levelsBeta-endorphin levelsEarly-onset patientsCerebrospinal fluid levelsLate-onset patientsCentral neurotransmitter systemsCSF monoamine metabolitesDopamine metabolite HVAAlcohol cue exposureAlcohol-dependent individualsCue-Induced CravingAlcohol cue reactivityLumbar punctureMetabolite HVANeurotransmitter systemsMonoaminergic dysregulationMetabolite MHPGCSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls
Petrakis I, Trevisan L, D'Souza C, Gil R, Krasnicki S, Webb E, Heninger G, Cooney N, Krystal J. CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls. Alcohol Clinical And Experimental Research 1999, 23: 1336. DOI: 10.1097/00000374-199908000-00007.Peer-Reviewed Original ResearchAlcohol-dependent patientsHealthy controlsEndorphin levelsCSF levelsMonoamine metabolitesCSF measuresHealthy subjectsNorepinephrine metabolite MHPGLower CSF levelsBeta-endorphin levelsEarly-onset patientsCerebrospinal fluid levelsLate-onset patientsCentral neurotransmitter systemsCSF monoamine metabolitesDopamine metabolite HVAAlcohol cue exposureAlcohol-dependent individualsAlcohol cue reactivityLumbar punctureBackground abnormalitiesMetabolite HVANeurotransmitter systemsMonoaminergic dysregulationMetabolite MHPG
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