2024
Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial
Sloshower J, Zeifman R, Guss J, Krause R, Safi-Aghdam H, Pathania S, Pittman B, D’Souza D. Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial. Scientific Reports 2024, 14: 8833. PMID: 38632313, PMCID: PMC11024097, DOI: 10.1038/s41598-024-58318-x.Peer-Reviewed Original ResearchConceptsPsilocybin-assisted therapyPsychological flexibilityDepression severityModerate to severe MDDSpectrum of neuropsychiatric conditionsTarget psychological flexibilityIncrease psychological flexibilityMental health conditionsManualized psychotherapyPsilocybin treatmentSevere MDDDepressive disorderExperiential acceptanceCommitment therapyDosing sessionsNeuropsychiatric conditionsPsychedelic trialsPlacebo-controlled trialWithin-subjectMDDPsilocybinAdministered placeboPlacebo-controlledDepressionClinical samplesPsilocybin 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 participantsWeeksSerotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile
Holze F, Singh N, Liechti M, D'Souza D. Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2024, 9: 472-489. PMID: 38301886, DOI: 10.1016/j.bpsc.2024.01.007.Peer-Reviewed Original ResearchConceptsSerotonergic psychedelicsSerotonin 2A receptor agonistPsychedelic effectsPsychedelic compoundsReceptor agonistsReview of efficacyPsychedelicsReceptor profilePsilocybinTherapeutic indicationsTherapeutic potentialPotential treatmentBinding profilesTherapeutic useClinical researchSerotonergicSerotoninPharmacokineticsMescalineDepressionEfficacyEffective durationAgonistsLSDResearchPsychopharmacological Treatment of Schizophrenia
Singh N, Ganesh S, D'Souza D. Psychopharmacological Treatment of Schizophrenia. 2024 DOI: 10.1016/b978-0-323-95702-1.00177-9.Peer-Reviewed Original ResearchAntipsychotic drugsPositive symptoms of schizophreniaPharmacological treatment of schizophreniaTreatment-resistant schizophreniaPharmacological treatmentSymptoms of schizophreniaTreatment of schizophreniaAcute psychotic episodeNeuroleptic malignant syndromeNegative symptomsPositive symptomsExtrapyramidal symptomsPsychotic episodeCognitive deficitsCognitive symptomsMalignant syndromeSchizophreniaPrevent relapseSide effectsMaintenance treatmentLong-actingDopamineAssociated with significant side effectsMedication adherenceProportion of patients
2023
The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J
Toyonaga T, Khattar N, Wu Y, Lu Y, Naganawa M, Gallezot J, Matuskey D, Mecca A, Pittman B, Dias M, Nabulsi N, Finnema S, Chen M, Arnsten A, Radhakrishnan R, Skosnik P, D’Souza D, Esterlis I, Huang Y, van Dyck C, Carson R. The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 51: 1012-1022. PMID: 37955791, DOI: 10.1007/s00259-023-06487-8.Peer-Reviewed Original ResearchSynaptic densityAge-related decreaseMagnetic resonance imagingBlood flowAge-related synaptic lossGray matter volume lossSynaptic density lossPositron emission tomography (PET) ligandSynaptic vesicle glycoprotein 2AVivo PET measurementsMedial occipital cortexGray matter volumeAge-related neurodegenerationGray matter regionsCognitive normal subjectsAge-related changesSynaptic lossNerve terminalsWide age rangeOccipital cortexTomography ligandNormal subjectsGM volumeAge-related functional lossesMatter volumeDysregulation 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 researchSub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms
Skosnik P, Sloshower J, Safi-Aghdam H, Pathania S, Syed S, Pittman B, D’Souza D. Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms. Journal Of Psychopharmacology 2023, 37: 687-697. PMID: 37392016, DOI: 10.1177/02698811231179800.Peer-Reviewed Original ResearchConceptsAntidepressant effectsTheta powerMajor depressive disorderEffects of psilocybinSub-acute effectsLong-term alterationsMeasures of depressionSingle doseDepressive disorderMajor depressionDepressive symptomsPlaceboSymptoms 2Depression symptomsEEG theta powerNeural plasticityNeuroplasticityEEG biomarkersSymptomsSerotonergic psychedelicsPotential mechanismsDepressionSustained changesElectroencephalographic correlatesPsilocybinThe Acute Effects of Cannabinoids in Patients with Psychotic Illness
Ganesh S, Henquet C, Sewell R, Kuepper R, Ranganathan M, D’Souza D. The Acute Effects of Cannabinoids in Patients with Psychotic Illness. 2023, 225-239. DOI: 10.1017/9781108943246.023.Peer-Reviewed Original ResearchMental illnessMental health teamsHealth policy implicationsHigh-potency cannabisStages of neurodevelopmentPotential adverse effectsAcute effectsHealth teamsPsychotic illnessImpact of exposureCannabis dependenceAdverse effectsIllnessCannabisCannabinoidsSynthetic cannabinoidsPsychosisNew research findingsAssociationComplex associationPatientsNeurodevelopmentPutative modelSchizophreniaCannabis Causes Positive, Negative, and Cognitive Symptoms and Produces Impairments in Electrophysiological Indices of Information Processing
Martin A, Ranganathan M, D’Souza D. Cannabis Causes Positive, Negative, and Cognitive Symptoms and Produces Impairments in Electrophysiological Indices of Information Processing. 2023, 156-166. DOI: 10.1017/9781108943246.017.Peer-Reviewed Original ResearchMental illnessMental health teamsHealth policy implicationsHigh-potency cannabisStages of neurodevelopmentPotential adverse effectsHealth teamsImpact of exposureCognitive symptomsCannabis dependenceAdverse effectsCannabisSynthetic cannabinoidsIllnessPsychosisCannabinoidsElectrophysiological indicesNew research findingsAssociationComplex associationSymptomsPutative modelNeurodevelopmentSchizophreniaImpairmentCannabis, cannabinoids and psychosis: a balanced view
D'Souza D. Cannabis, cannabinoids and psychosis: a balanced view. World Psychiatry 2023, 22: 231-232. PMID: 37159370, PMCID: PMC10168157, DOI: 10.1002/wps.21075.Peer-Reviewed Original ResearchRandomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia
Surti T, Ranganathan M, Johannesen J, Gueorguieva R, Deaso E, Kenney J, Krystal J, D'Souza D. Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia. Schizophrenia Research 2023, 256: 36-43. PMID: 37141764, PMCID: PMC10257994, DOI: 10.1016/j.schres.2023.04.010.Peer-Reviewed Original ResearchConceptsGlycine transporter 1Cytochrome P450 2D6 extensive metabolizersGlyT1 inhibitorsWeeks of washoutWeeks of CTMedication adherenceReceptor hypofunctionImpaired neuroplasticityPharmacodynamic variabilityNMDAR functionExtensive metabolizersTreatment periodPsychotic symptomsStable outpatientsCognitive impairmentGlyT1 occupancyTransporter 1CTNeuroplasticityCognitive training strategiesSchizophreniaComputerized CTCognitive performanceAugmentation studiesGreater improvementPeripheral 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 ResearchConceptsNeuron-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 studyPreliminary study of the interactive effects of THC and ethanol on self-reported ability and simulated driving, subjective effects, and cardiovascular responses
Schnakenberg Martin A, Flynn L, Sefik E, Luddy C, Cortes-Briones J, Skosnik P, Pittman B, Ranganathan M, D’Souza D. Preliminary study of the interactive effects of THC and ethanol on self-reported ability and simulated driving, subjective effects, and cardiovascular responses. Psychopharmacology 2023, 240: 1235-1246. PMID: 37045988, DOI: 10.1007/s00213-023-06356-0.Peer-Reviewed Original ResearchConceptsSubjective effectsOral tetrahydrocannabinolSelf-reported abilityEffects of cannabisInfluence of tetrahydrocannabinolCause of morbiditySimulated drivingFeeling statesBlood alcohol levelsMotor vehicle accidentsAlcohol-related motor vehicle accidentsCardiovascular responsesIntravenous ethanolHealthy humansHeart rateVehicle accidentsAlcohol levelsInteractive effectsTetrahydrocannabinolPhysiological effectsSignificant differencesDrivingAbilityPreliminary studyRationaleDrugPsilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial
Sloshower J, Skosnik P, Safi-Aghdam H, Pathania S, Syed S, Pittman B, D’Souza D. Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial. Journal Of Psychopharmacology 2023, 37: 698-706. PMID: 36938991, DOI: 10.1177/02698811231154852.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAntidepressant effectsDepressive disorderSevere major depressive disorderPsilocybin-assisted therapyEarly phase studiesQuality of lifeClinical improvementDosing sessionsMajor depressionPsilocybin administrationPlacebo effectPsychotherapeutic supportPlaceboTherapy effectsStudy periodPsychotherapy studiesFurther studiesSignificant differencesDepressionDosingTherapyHigh rateEffect sizeDegree of change
2022
Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users
Johnson E, Colbert S, Jeffries P, Tillman R, Bigdeli T, Karcher N, Chan G, Kuperman S, Meyers J, Nurnberger J, Plawecki M, Degenhardt L, Martin N, Kamarajan C, Schuckit M, Murray R, Dick D, Edenberg H, D’Souza D, Di Forti M, Porjesz B, Nelson E, Agrawal A. Associations Between Cannabis Use, Polygenic Liability for Schizophrenia, and Cannabis-related Experiences in a Sample of Cannabis Users. Schizophrenia Bulletin 2022, 49: 778-787. PMID: 36545904, PMCID: PMC10154717, DOI: 10.1093/schbul/sbac196.Peer-Reviewed Original ResearchConceptsCannabis useAlcohol use disorderCognitive difficultiesSchizophrenia polygenic risk scoresFirst cannabis useDaily cannabis useCannabis usersSocial withdrawalUnusual experiencesCannabis involvementPolygenic risk scoresExpected directionGenetic riskUse disordersIndependent replication sampleLike experiencesGenetic liabilityCannabisSchizophreniaPolygenic riskPolygenic liabilityReplication sampleExperienceAnalytic sampleDisordersThe therapeutic potential of psychedelics
Schindler E, D'Souza D. The therapeutic potential of psychedelics. Science 2022, 378: 1051-1053. PMID: 36480624, DOI: 10.1126/science.abn5486.Peer-Reviewed Original ResearchExploratory investigation of a patient‐informed low‐dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double‐blind, placebo‐controlled trial
Schindler E, Sewell R, Gottschalk C, Luddy C, Flynn L, Zhu Y, Lindsey H, Pittman B, Cozzi N, D'Souza D. Exploratory investigation of a patient‐informed low‐dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double‐blind, placebo‐controlled trial. Headache The Journal Of Head And Face Pain 2022, 62: 1383-1394. PMID: 36416492, DOI: 10.1111/head.14420.Peer-Reviewed Original ResearchConceptsAttacks/weekPulse regimenCluster headachePsychotropic effectsAttack frequencyPlacebo-controlled studyPlacebo-controlled trialSerious adverse eventsEffects of psilocybinEffect sizeChronic participantsEfficacy outcomesAdverse eventsModerate effect sizeHeadache burdenHeadache disordersTherapeutic effectHeadache diaryPsilocybin administrationDrug sessionsExperimental drugsRegimenPsilocybin-containing mushroomsDefinitive studiesFinal analysisAge, 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 ResearchPenetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System
Bigdeli TB, Voloudakis G, Barr PB, Gorman BR, Genovese G, Peterson RE, Burstein DE, Velicu VI, Li Y, Gupta R, Mattheisen M, Tomasi S, Rajeevan N, Sayward F, Radhakrishnan K, Natarajan S, Malhotra AK, Shi Y, Zhao H, Kosten TR, Concato J, O’Leary T, Przygodzki R, Gleason T, Pyarajan S, Brophy M, Huang GD, Muralidhar S, Gaziano JM, Aslan M, Fanous AH, Harvey PD, Roussos P, Aslan M, Antonelli M, de Asis M, Bauer M, Brophy M, Concato J, Cunningham F, Freedman R, Gaziano M, Gleason T, Harvey P, Huang G, Kelsoe J, Kosten T, Lehner T, Lohr J, Marder S, Miller P, O Leary T, Patterson T, Peduzzi P, Przygodski R, Siever L, Sklar P, Strakowski S, Zhao H, Fanous A, Farwell W, Malhorta A, Mane S, Palacios P, Bigdeli T, Corsey M, Zaluda L, Johnson J, Sueiro M, Cavaliere D, Jeanpaul V, Maffucci A, Mancini L, Deen J, Muldoon G, Whitbourne S, Canive J, Adamson L, Calais L, Fuldauer G, Kushner R, Toney G, Lackey M, Mank A, Mahdavi N, Villarreal G, Muly E, Amin F, Dent M, Wold J, Fischer B, Elliott A, Felix C, Gill G, Parker P, Logan C, McAlpine J, DeLisi L, Reece S, Hammer M, Agbor-Tabie D, Goodson W, Aslam M, Grainger M, Richtand N, Rybalsky A, Al Jurdi R, Boeckman E, Natividad T, Smith D, Stewart M, Torres S, Zhao Z, Mayeda A, Green A, Hofstetter J, Ngombu S, Scott M, Strasburger A, Sumner J, Paschall G, Mucciarelli J, Owen R, Theus S, Tompkins D, Potkin S, Reist C, Novin M, Khalaghizadeh S, Douyon R, Kumar N, Martinez B, Sponheim S, Bender T, Lucas H, Lyon A, Marggraf M, Sorensen L, Surerus C, Sison C, Amato J, Johnson D, Pagan-Howard N, Adler L, Alerpin S, Leon T, Mattocks K, Araeva N, Sullivan J, Suppes T, Bratcher K, Drag L, Fischer E, Fujitani L, Gill S, Grimm D, Hoblyn J, Nguyen T, Nikolaev E, Shere L, Relova R, Vicencio A, Yip M, Hurford I, Acheampong S, Carfagno G, Haas G, Appelt C, Brown E, Chakraborty B, Kelly E, Klima G, Steinhauer S, Hurley R, Belle R, Eknoyan D, Johnson K, Lamotte J, Granholm E, Bradshaw K, Holden J, Jones R, Le T, Molina I, Peyton M, Ruiz I, Sally L, Tapp A, Devroy S, Jain V, Kilzieh N, Maus L, Miller K, Pope H, Wood A, Meyer E, Givens P, Hicks P, Justice S, McNair K, Pena J, Tharp D, Davis L, Ban M, Cheatum L, Darr P, Grayson W, Munford J, Whitfield B, Wilson E, Melnikoff S, Schwartz B, Tureson M, D Souza D, Forselius K, Ranganathan M, Rispoli L, Sather M, Colling C, Haakenson C, Kruegar D, Muralidhar S, Ramoni R, Breeling J, Chang K, O Donnell C, Tsao P, Moser J, Brewer J, Warren S, Argyres D, Stevens B, Humphries D, Do N, Shayan S, Nguyen X, Pyarajan S, Cho K, Hauser E, Sun Y, Wilson P, McArdle R, Dellitalia L, Harley J, Whittle J. Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System. JAMA Psychiatry 2022, 79: 1092-1101. PMID: 36103194, PMCID: PMC9475441, DOI: 10.1001/jamapsychiatry.2022.2742.Peer-Reviewed Original ResearchDiagnosis of schizophreniaPolygenic risk scoresBipolar disorderHealth care systemElectronic health recordsBilling codesRisk scoreUS Veterans Affairs Health Care SystemClinical InterviewVeterans Health Administration health care systemVeterans Affairs Health Care SystemDisorder-specific genetic factorsVeterans Health Administration electronic health recordsCare systemICD-9/10 codesMajor depression polygenic risk scoresSerious mental illnessEuropean ancestryDepression polygenic risk scoresPhysical health problemsAfrican ancestryUS veteransMajor depressionMillion Veteran ProgramMAIN OUTCOMEIllness Phase as a Key Assessment and Intervention Window for Psychosis
Kohler C, Wolf D, Abi-Dargham A, Anticevic A, Cho Y, Fonteneau C, Gil R, Girgis R, Gray D, Grinband J, Javitch J, Kantrowitz J, Krystal J, Lieberman J, Murray J, Ranganathan M, Santamauro N, Van Snellenberg J, Tamayo Z, Group T, 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, Gur R, Gur R, Calkins M. Illness Phase as a Key Assessment and Intervention Window for Psychosis. Biological Psychiatry Global Open Science 2022, 3: 340-350. PMID: 37519466, PMCID: PMC10382701, DOI: 10.1016/j.bpsgos.2022.05.009.Peer-Reviewed Original ResearchIllness phasePotential critical windowsPhase-specific biomarkersDopaminergic abnormalitiesFunctional outcomeSpecialty careSymptom assessmentIllness stageChronic illnessClinical assessmentIllness trajectoryNeurophysiological biomarkersFunctional abnormalitiesClinical careEarly psychosisMemory dysfunctionPsychotic disordersTreatment targetsAllostatic adaptationIntervention windowClinical programsBrain developmentCritical windowDysfunctionIllness