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 ResearchPsilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial
Schindler E, Sewell R, Gottschalk C, Flynn L, Zhu Y, Pittman B, Cozzi N, D'Souza D. Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial. Journal Of The Neurological Sciences 2024, 460: 122993. PMID: 38581739, DOI: 10.1016/j.jns.2024.122993.Peer-Reviewed Original ResearchConceptsAttack frequencyCluster headacheCluster headache attack frequencyExtension phaseEffects of repeated treatmentReduction of attack frequencyPlacebo-controlled studyHeadache attack frequencyAdministration of psilocybinRandomized controlled trialsDouble-blindPsilocybin administrationPulse regimenAdverse eventsPulse regimensHeadache diaryTherapeutic efficacyDrug sessionsPulse administrationHeadacheStudy participantsWeeks
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
Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia
Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME, Cho YT, Fonteneau C, Gil R, Girgis R, Gur RE, Gur RC, Grinband J, Kantrowitz J, Kohler C, Krystal J, Murray J, Ranganathan M, Santamauro N, Van Snellenberg J, Tamayo Z, Wolf D, D’Souza D, Srihari V, Gueorguieva R, Patel P, Forselius-Bielen K, Lu J, Butler A, Fram G, Afriyie-Agyemang Y, Selloni A, Cadavid L, Gomez-Luna S, Gupta A, Radhakrishnan R, Rashid A, Aker R, Abrahim P, Nia A, Surti T, Kegeles L, Carlson M, Goldberg T, Gangwisch J, Benedict E, Govil P, Brazis S, Mayer M, de la Garrigue N, Fallon N, Baumvoll T, Abeykoon S, Perlman G, Bobchin K, Elliott M, Schmidt L, Rush S, Port A, Heffernan Z, Laney N, Kantor J, Hohing T, Gray D, Lieberman J. Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia Bulletin 2021, 48: 199-210. PMID: 34423843, PMCID: PMC8781338, DOI: 10.1093/schbul/sbab095.Peer-Reviewed Original ResearchConceptsCortical dopamine neurotransmissionPositive allosteric modulationImportant therapeutic targetPF-06412562Dopaminergic receptorsD1R stimulationDA levelsTolerable dosesLevel of stimulationDopamine neurotransmissionReceptor stimulationTherapeutic targetPartial agonistCognitive deficitsBiased agonismFull agonismTarget engagementAllosteric modulationNew drugsStimulationPoor bioavailabilitySchizophreniaOptimal stimulationDrugsExpression levelsIdentifying 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 ligandsWeeksAdministrationIn an exploratory randomized, double-blind, placebo-controlled, cross-over study, psychoactive doses of intravenous delta-9-tetrahydrocannabinol fail to produce antinociceptive effects in healthy human volunteers
Schindler EAD, Schnakenberg Martin AM, Sewell RA, Ranganathan M, DeForest A, Pittman BP, Perrino A, D’Souza D. In an exploratory randomized, double-blind, placebo-controlled, cross-over study, psychoactive doses of intravenous delta-9-tetrahydrocannabinol fail to produce antinociceptive effects in healthy human volunteers. Psychopharmacology 2020, 237: 3097-3107. PMID: 32632491, DOI: 10.1007/s00213-020-05595-9.Peer-Reviewed Original ResearchConceptsCapsaicin-induced hyperalgesiaCross-over studyHealthy human subjectsIntravenous THCAcute painAntinociceptive effectDrug effectsDrug AdministrationHuman subjectsDose-related mannerPeak drug effectHealthy human volunteersSignificant antinociceptive propertiesRationaleAnimal studiesElectrical painPain conditionsPain managementChemical painPain ratingsAntinociceptive propertiesHealthy volunteersPsychoactive dosesAcute chemicalHuman studiesCognitive alterationsPsychosis-Relevant Effects of Intravenous Delta-9-Tetrahydrocannabinol: A Mega Analysis of Individual Participant-Data from Human Laboratory Studies
Ganesh S, Cortes-Briones J, Ranganathan M, Radhakrishnan R, Skosnik PD, D’Souza D. Psychosis-Relevant Effects of Intravenous Delta-9-Tetrahydrocannabinol: A Mega Analysis of Individual Participant-Data from Human Laboratory Studies. The International Journal Of Neuropsychopharmacology 2020, 23: 559-570. PMID: 32385508, PMCID: PMC7710917, DOI: 10.1093/ijnp/pyaa031.Peer-Reviewed Original ResearchConceptsHuman laboratory studiesHealthy human volunteersPositive symptomsTHC dosePsychotomimetic effectsHuman volunteersPsychosis-like effectsNegative Syndrome ScaleProfile of symptomsCrossover studyIntravenous administrationMotor retardationHealthy individualsSyndrome ScaleSymptomsNegative syndromeSomatic concernsSubstance useConceptual disorganizationFrequent cannabisMultiple studiesMeaningful increase
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 effortsTest-retest reliability of time-frequency measures of auditory steady-state responses in patients with schizophrenia and healthy controls
Roach BJ, D'Souza DC, Ford JM, Mathalon DH. Test-retest reliability of time-frequency measures of auditory steady-state responses in patients with schizophrenia and healthy controls. NeuroImage Clinical 2019, 23: 101878. PMID: 31228795, PMCID: PMC6587022, DOI: 10.1016/j.nicl.2019.101878.Peer-Reviewed Original ResearchEffects 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 ResearchThe 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 ScaleCannabinoid 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