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
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 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 individualsHaloperidolGrey 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 ResearchMeSH KeywordsAdolescentBrainCerebellumFemaleGray MatterGyrus CinguliHumansMaleMarijuana SmokingTemporal LobeConceptsGray 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
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 stateSchizophrenia
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 abnormalities
2016
Feasibility 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
Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine
Ahn KH, Sewell A, Elander J, Pittman B, Ranganathan M, Gunduz-Bruce H, Krystal J, D'Souza DC. Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine. Neuropsychopharmacology 2015, 40: 2822-2831. PMID: 25953357, PMCID: PMC4864658, DOI: 10.1038/npp.2015.132.Peer-Reviewed Original ResearchConceptsGABA deficitHealthy subjectsPsychotomimetic effectsIntravenous infusionSchizophrenia patientsPANSS positive symptoms subscaleDouble-blind crossover designStriatal dopamine releasePositive symptom subscaleAdministration of drugsDose of AMPHPartial inverse agonistSubclinical responsePharmacokinetic interactionsSubthreshold doseDopamine releaseBenzodiazepine receptorsSymptom subscalesCrossover designCADSS scoresPositive symptomsAMPHInverse agonistSubjective effectsTest dayΔ9-THC Disrupts Gamma (γ)-Band Neural Oscillations in Humans
Cortes-Briones J, Skosnik PD, Mathalon D, Cahill J, Pittman B, Williams A, Sewell RA, Ranganathan M, Roach B, Ford J, D'Souza DC. Δ9-THC Disrupts Gamma (γ)-Band Neural Oscillations in Humans. Neuropsychopharmacology 2015, 40: 2124-2134. PMID: 25709097, PMCID: PMC4613601, DOI: 10.1038/npp.2015.53.Peer-Reviewed Original ResearchConceptsAuditory steady-state responseΔ9-THCHz stimulationIntertrial coherenceDose-related effectsNeural oscillationsNegative Syndrome ScalePsychophysiological alterationsAcute effectsPsychotic disordersAnimal studiesSyndrome ScalePANSS subscalesRecent usersBehavioral effectsTotal scoreEvoked powerCannabinoidsCounterbalanced designTrend levelΓ oscillationsTest dayBand oscillationsHz conditionStimulationThe Psychosis-like Effects of Δ9-Tetrahydrocannabinol Are Associated With Increased Cortical Noise in Healthy Humans
Cortes-Briones JA, Cahill JD, Skosnik PD, Mathalon DH, Williams A, Sewell RA, Roach BJ, Ford JM, Ranganathan M, D’Souza D. The Psychosis-like Effects of Δ9-Tetrahydrocannabinol Are Associated With Increased Cortical Noise in Healthy Humans. Biological Psychiatry 2015, 78: 805-813. PMID: 25913109, PMCID: PMC4627857, DOI: 10.1016/j.biopsych.2015.03.023.Peer-Reviewed Original ResearchConceptsPsychosis-like effectsPsychosis-like symptomsPsychotomimetic effectsNegative-like symptomsActive drug conditionsNeural noiseDose-related effectsDose-related mannerRandom neural activityDose-dependent mannerPrincipal active constituentHealthy humansPsychotic disordersCortical noiseDrug conditionsSymptomsΔ9-tetrahydrocannabinolBaseline periodDisorganization symptomsNeural activityCounterbalanced designTest dayActive constituentsOddball taskTHCGABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC
Radhakrishnan R, Skosnik PD, Cortes-Briones J, Sewell RA, Carbuto M, Schnakenberg A, Cahill J, Bois F, Gunduz-Bruce H, Pittman B, Ranganathan M, D'Souza DC. GABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC. Neuropsychopharmacology 2015, 40: 2047-2056. PMID: 25728472, PMCID: PMC4839528, DOI: 10.1038/npp.2015.58.Peer-Reviewed Original Research
2014
Disrupted Gamma-Band Neural Oscillations During Coherent Motion Perception in Heavy Cannabis Users
Skosnik PD, Krishnan GP, D'Souza DC, Hetrick WP, O'Donnell BF. Disrupted Gamma-Band Neural Oscillations During Coherent Motion Perception in Heavy Cannabis Users. Neuropsychopharmacology 2014, 39: 3087-3099. PMID: 24990428, PMCID: PMC4229582, DOI: 10.1038/npp.2014.166.Peer-Reviewed Original Research
2012
Acute effects of THC on time perception in frequent and infrequent cannabis users
Sewell RA, Schnakenberg A, Elander J, Radhakrishnan R, Williams A, Skosnik PD, Pittman B, Ranganathan M, D’Souza D. Acute effects of THC on time perception in frequent and infrequent cannabis users. Psychopharmacology 2012, 226: 401-413. PMID: 23179965, PMCID: PMC3581701, DOI: 10.1007/s00213-012-2915-6.Peer-Reviewed Original ResearchConceptsCannabis smokersAcute effectsFrequent cannabis smokersPlacebo-controlled studyCannabis usersChronic cannabis smokersInfrequent cannabis usersWhole-plant cannabisChronic cannabis useResultsAll dosesVariable pharmacokineticsBlunted responseSubjects three timesHigh dosesTHC effectsFrequent cannabis usersCannabis useInternal clock speedΔ9-tetrahydrocannabinolSmall sample sizeDosesFrequent cannabisThree timesTest daySmokersGlycine treatment of the risk syndrome for psychosis: Report of two pilot studies
Woods SW, Walsh BC, Hawkins KA, Miller TJ, Saksa JR, D'Souza DC, Pearlson GD, Javitt DC, McGlashan TH, Krystal JH. Glycine treatment of the risk syndrome for psychosis: Report of two pilot studies. European Neuropsychopharmacology 2012, 23: 931-940. PMID: 23089076, PMCID: PMC4028140, DOI: 10.1016/j.euroneuro.2012.09.008.Peer-Reviewed Original ResearchConceptsPilot studyRisk syndromeSyndrome patientsNegative symptomsShort-term pilot studyEffect sizeAdjunctive antipsychotic medicationOpen-label studyPatients meeting criteriaNMDA receptor functionDurability of effectPsychosis risk symptomsGlycine site agonistsGroup effect sizesWeeks of evaluationAntipsychotic medicationSyndrome subjectsPromising effect sizesTreatment needsLarge effect sizesMeeting criteriaCognitive impairmentReduced symptomsReceptor functionSymptomsNicotine Fails to Attenuate Ketamine-Induced Cognitive Deficits and Negative and Positive Symptoms in Humans: Implications for Schizophrenia
D'Souza DC, Ahn K, Bhakta S, Elander J, Singh N, Nadim H, Jatlow P, Suckow RF, Pittman B, Ranganathan M. Nicotine Fails to Attenuate Ketamine-Induced Cognitive Deficits and Negative and Positive Symptoms in Humans: Implications for Schizophrenia. Biological Psychiatry 2012, 72: 785-794. PMID: 22717030, DOI: 10.1016/j.biopsych.2012.05.009.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAttentionCognitionCognition DisordersCross-Over StudiesDouble-Blind MethodDrug InteractionsExecutive FunctionHumansInhibition, PsychologicalKetamineMemoryMiddle AgedMotor SkillsNicotinePsychiatric Status Rating ScalesPsychomotor PerformanceReaction TimeRecognition, PsychologySchizophreniaConceptsCognitive deficitsPositive symptomsExecutive functionResponse inhibitionKetamine-induced cognitive deficitsChoice reaction time taskSpeed of processingReaction time taskReaction timeVisual memoryEmotion recognitionImmediate recallSustained attentionTime taskFeeling statesPerceptual alterationsSerial processingEffects of nicotineNegative symptomsMemoryBehavioral effectsDeficitsInteractive effectsNicotine infusionTest dayDose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans
D'Souza DC, Fridberg DJ, Skosnik PD, Williams A, Roach B, Singh N, Carbuto M, Elander J, Schnakenberg A, Pittman B, Sewell RA, Ranganathan M, Mathalon D. Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans. Neuropsychopharmacology 2012, 37: 1632-1646. PMID: 22334121, PMCID: PMC3358754, DOI: 10.1038/npp.2012.8.Peer-Reviewed Original ResearchConceptsRecent cannabis usersPerceptual alterationsERP componentsCannabis usersEvent-related potential taskSensory ERP componentsCannabis Use StatusModulation of eventsΔ9-THCProperties of cannabisContext updatingNeural correlatesP3b amplitudeTarget stimuliPsychophysiological indicesCortical processesP300b amplitudesProcessing speedCognitive deficitsPsychophysiological dataInformation processingAutomatic orientationCounterbalanced designSubjective effectsPotential tasksNaltrexone 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
The 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
High dose D-serine in the treatment of schizophrenia
Kantrowitz JT, Malhotra AK, Cornblatt B, Silipo G, Balla A, Suckow RF, D'Souza C, Saksa J, Woods SW, Javitt DC. High dose D-serine in the treatment of schizophrenia. Schizophrenia Research 2010, 121: 125-130. PMID: 20541910, PMCID: PMC3111070, DOI: 10.1016/j.schres.2010.05.012.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnalysis of VarianceAntipsychotic AgentsChi-Square DistributionCognition DisordersDose-Response Relationship, DrugFemaleFollow-Up StudiesHumansMaleMiddle AgedNeuropsychological TestsPsychiatric Status Rating ScalesRegression AnalysisSchizophreniaSerineTreatment OutcomeYoung AdultConceptsD-serineBrain N-methyl-D-aspartate receptorsPlasma D-serine levelsN-methyl-D-aspartate receptorsSafety of dosesSignificant dose-dependent increaseDouble-blind investigationOpen-label trialDose-escalation studyDouble-blind studyLarge effect size improvementsTreatment of schizophreniaD-serine levelsPotential novel treatmentPharmacokinetics/pharmacodynamicsDose-dependent increaseNon-significant improvementEffect size improvementsMedication phasePersistent symptomsEscalation studyBrain levelsPlasma levelsPK analysisNeurocognitive dysfunction