2025
Cannabinoid 1 receptor availability in posttraumatic stress disorder: A positron emission tomography study
Korem N, Bassir Nia A, Hillmer A, D’Souza D, Nabulsi N, Ropchan J, Huang Y, Cosgrove K, Levy I, Pietrzak R, Harpaz-Rotem I. Cannabinoid 1 receptor availability in posttraumatic stress disorder: A positron emission tomography study. Translational Psychiatry 2025, 15: 310. DOI: 10.1038/s41398-025-03519-9.Peer-Reviewed Original ResearchPathophysiology of posttraumatic stress disorderEmotional numbing symptomsCB1R availabilityPosttraumatic stress disorderEndocannabinoid systemStress disorderPositron emission tomographyTrauma-exposed participantsEndocannabinoid system's rolePositron emission tomography studiesCannabinoid receptor 1Emission tomography studiesMulti-faceted disorderFear learningCB1RSymptom expressionHealthy controlsCannabinoidDisordersTomography studiesEmission tomographyPreclinical studiesSymptomsHigher levelsReceptor 1611. Cannabinoid 1 Receptor Availability in Men With Opioid Use Disorder: A Positron Emission Tomography Study
Nia A, Hillmer A, Aghaei A, Pittman B, Huang H, Nabulsi N, D'Souza D. 611. Cannabinoid 1 Receptor Availability in Men With Opioid Use Disorder: A Positron Emission Tomography Study. Biological Psychiatry 2025, 97: s350. DOI: 10.1016/j.biopsych.2025.02.850.Peer-Reviewed Original ResearchPsilocybin’s Effects on Headache Frequency are Not Related to Acute Psychedelic Effects or Measures of Mental Health: Secondary Analysis of Clinical Trials in Migraine and Cluster Headache (P7-12.001)
Schindler E, Gottschalk C, D'Souza D. Psilocybin’s Effects on Headache Frequency are Not Related to Acute Psychedelic Effects or Measures of Mental Health: Secondary Analysis of Clinical Trials in Migraine and Cluster Headache (P7-12.001). Neurology 2025, 104 DOI: 10.1212/wnl.0000000000210945.Peer-Reviewed Original ResearchAddressing blinding in classic psychedelic studies with innovative active placebos
Aday J, Simonsson O, Schindler E, D’Souza D. Addressing blinding in classic psychedelic studies with innovative active placebos. The International Journal Of Neuropsychopharmacology 2025, 28: pyaf023. PMID: 40183712, PMCID: PMC12038243, DOI: 10.1093/ijnp/pyaf023.Peer-Reviewed Original ResearchConceptsActive placeboClassic psychedelicsPsychedelic studiesAcute psychoactive effectsModerate-to-high dosesPlacebo conditionNeuropsychiatric disordersPsychoactive effectsAcute physiological effectsTherapeutic effectPsychedelicsLow-dose administrationBlind integrationLack of therapeutic effectAcute effectsReview interventionsPlaceboShort-actingClinical trialsPharmacological agentsImproved blindingAncillary strategiesTrialsPhysiological effectsDisordersGenerating synthetic brain PET images of synaptic density based on MR T1 images using deep learning
Zheng X, Worhunsky P, Liu Q, Guo X, Chen X, Sun H, Zhang J, Toyonaga T, Mecca A, O’Dell R, van Dyck C, Angarita G, Cosgrove K, D’Souza D, Matuskey D, Esterlis I, Carson R, Radhakrishnan R, Liu C. Generating synthetic brain PET images of synaptic density based on MR T1 images using deep learning. EJNMMI Physics 2025, 12: 30. PMID: 40163154, PMCID: PMC11958861, DOI: 10.1186/s40658-025-00744-5.Peer-Reviewed Original ResearchCannabis use disorderStructural similarity indexPET imagingImages of higher qualityMR-T1 imagesMean square errorUse disorderEncoder-decoderDeep learningCross-validation processData-driven approachDiagnostic categoriesLow-dose scansPredicted imageTemporal regionsBrain disordersGround truthT1-weighted MRISynaptic densityHuman brainSimilarity indexDisordersSevere neurological disordersTranslation accuracyNoise reduction
2024
Metabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use
Weiss E, Davis M, Asch R, D'Souza D, Cool R, Esterlis I. Metabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use. The International Journal Of Neuropsychopharmacology 2024, 27: pyae044. PMID: 39320043, PMCID: PMC11969217, DOI: 10.1093/ijnp/pyae044.Peer-Reviewed Original ResearchTrauma-related psychopathologyCannabis useDepressive symptomsPositron emission tomographyCross-diagnostic sampleMetabotropic glutamate receptor 5Treatment development effortsAssociated with depressive symptomsGlutamate receptor 5Cu groupSample of individualsAvailability in vivoFrontolimbic regionsGlutamatergic systemGlutamatergic neurotransmissionMGlu5PsychopathologyReceptor 5Intersection of traumaExploratory analysisCannabisEmission tomographySymptomsParticipantsVmPFCAmygdala 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 ResearchPsychological 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, 729-737. 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 correlatesPsilocybinCannabis 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 modelNeurodevelopmentSchizophreniaImpairmentThe 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, 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 studyRationaleDrug
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