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 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 durationAgonistsLSDResearch
2023
Dysregulation 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 correlatesPsilocybinRandomized 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 ResearchExploratory 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 rateSex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC)
Bassir Nia A, Orejarena MJ, Flynn L, Luddy C, D’Souza D, Skosnik PD, Pittman B, Ranganathan M. Sex differences in the acute effects of intravenous (IV) delta-9 tetrahydrocannabinol (THC). Psychopharmacology 2022, 239: 1621-1628. PMID: 35438304, PMCID: PMC11215802, DOI: 10.1007/s00213-022-06135-3.Peer-Reviewed Original ResearchConceptsRey Auditory Verbal Learning TaskPsychotomimetic States InventoryCognitive effectsAuditory Verbal Learning TaskSubjective effectsDelta-9-TetrahydrocannabinolSex differencesVerbal learning taskDissociative Symptoms ScaleFemale participantsMain psychoactive constituentSignificant main effectPerceptual alterationsLearning taskStates InventoryPsychoactive constituentSignificant sex differencesMain effectMale participantsVisual analog scaleSymptom ScaleTest dayEffects of cannabinoidsParticipantsPsychotomimetic effectsConsensus paper of the WFSBP task force on cannabis, cannabinoids and psychosis
D’Souza D, DiForti M, Ganesh S, George TP, Hall W, Hjorthøj C, Howes O, Keshavan M, Murray RM, Nguyen TB, Pearlson GD, Ranganathan M, Selloni A, Solowij N, Spinazzola E. Consensus paper of the WFSBP task force on cannabis, cannabinoids and psychosis. The World Journal Of Biological Psychiatry 2022, 23: 719-742. PMID: 35315315, DOI: 10.1080/15622975.2022.2038797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsWFSBP Task ForceRisk of psychosisAge of exposureRates of psychosisRecurrent psychosisTask ForceEndocannabinoid systemPsychosis outcomesConsensus paperHigh riskPsychotic disordersPsychotic statesPsychosisPotency of cannabisCriteria of causalityCannabisCannabinoidsLines of evidenceCannabis lawsRiskExposureDisordersEvidenceConfoundersIllnessDose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial
Abdallah CG, Roache JD, Gueorguieva R, Averill LA, Young-McCaughan S, Shiroma PR, Purohit P, Brundige A, Murff W, Ahn KH, Sherif MA, Baltutis EJ, Ranganathan M, D’Souza D, Martini B, Southwick SM, Petrakis IL, Burson RR, Guthmiller KB, López-Roca AL, Lautenschlager KA, McCallin JP, Hoch MB, Timchenko A, Souza SE, Bryant CE, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology 2022, 47: 1574-1581. PMID: 35046508, PMCID: PMC8767037, DOI: 10.1038/s41386-022-01266-9.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderClinical trialsOutcome measuresMontgomery-Åsberg Depression Rating ScaleSelf-report PTSD ChecklistÅsberg Depression Rating ScaleStress disorderPTSD symptomsAntidepressant-resistant symptomsPrevious antidepressant treatmentClinician-Administered PTSD ScaleMulti-center clinical trialRapid antidepressant effectsSecondary outcome measuresPrimary outcome measureSignificant dose-related effectsRole of ketamineDepression Rating ScaleDose-related effectsEffects of ketamineDSM-5Intravenous placeboDose ketamineTreatment discontinuationActive duty military
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 levelsDifferential Cognitive Performance in Females and Males with Regular Cannabis Use
Martin A, D’Souza D, Newman SD, Hetrick WP, O’Donnell B. Differential Cognitive Performance in Females and Males with Regular Cannabis Use. Journal Of The International Neuropsychological Society 2021, 27: 570-580. PMID: 34261548, PMCID: PMC8830784, DOI: 10.1017/s1355617721000606.Peer-Reviewed Original ResearchConceptsRegular cannabis useCannabis useCognitive measuresPsychomotor speedBiological sexHopkins Verbal Learning TestDifferential cognitive performanceNon-using peersVerbal Learning TestMeasures of intelligenceWechsler Abbreviated ScaleDigit symbol testGreatest group differencesVerbal learningDigit spanLearning TestCognitive performanceAbbreviated ScaleNeurocognitive deficitsCognitive deficitsSymbol testCannabis exposurePsychomotor performanceGroup differencesCognition