2022
Sex 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 effects
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 efforts
2018
Cannabinoid 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 subjects
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 taskTHC
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 daySmokersNicotine 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 dayNaltrexone 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
Preliminary Findings on the Interactive Effects of IV Ethanol and IV Nicotine on Human Behavior and Cognition: A Laboratory Study
Ralevski E, Perry EB, D’Souza D, Bufis V, Elander J, Limoncelli D, Vendetti M, Dean E, Cooper TB, McKee S, Petrakis I. Preliminary Findings on the Interactive Effects of IV Ethanol and IV Nicotine on Human Behavior and Cognition: A Laboratory Study. Nicotine & Tobacco Research 2011, 14: 596-606. PMID: 22180582, PMCID: PMC6281082, DOI: 10.1093/ntr/ntr258.Peer-Reviewed Original ResearchConceptsRey Auditory Verbal Learning TaskAuditory Verbal Learning TaskVerbal learning taskAcute intravenous alcoholSubjective alcohol effectsBiphasic Alcohol Effects ScaleAlcohol-induced deficitsAlcohol-induced impairmentDoses of alcoholActive nicotineInteractive effectsTest dayCognitive inhibitionVerbal learningCognitive performanceLearning taskSubjective intoxicationAlcohol effectsHuman behaviorNicotine effectsIntravenous alcoholAlcohol infusionManner oneSubjective effectsCognitionGlutamatergic Modulation of Auditory Information Processing in the Human Brain
Gunduz-Bruce H, Reinhart RM, Roach BJ, Gueorguieva R, Oliver S, D'Souza DC, Ford JM, Krystal JH, Mathalon DH. Glutamatergic Modulation of Auditory Information Processing in the Human Brain. Biological Psychiatry 2011, 71: 969-977. PMID: 22036036, PMCID: PMC3290754, DOI: 10.1016/j.biopsych.2011.09.031.Peer-Reviewed Original ResearchConceptsN-acetylcysteineAuditory mismatch negativityReceptor antagonistN-methyl-D-aspartate receptor antagonistAspartate glutamate receptor antagonistOral N-acetylcysteinePlacebo-controlled studyGlutamate receptor antagonistsEffects of ketamineInfusion of salineMismatch negativityTest dayMMN amplitudeCystine-glutamate exchangerAuditory information processingP300 event-related potentialGlutamatergic modulationCognitive enhancing agentsEvent-related potentialsKetamine effectsHealthy volunteersHealthy humansSchizophrenia patientsPositive symptomsKetamineThe 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
2006
Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects
Neumeister A, Carson R, Henry S, Planeta-Wilson B, Binneman B, Maguire RP, Luckenbaugh DA, D'Souza C, Krystal JH, Frost JJ. Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects. Journal Of Clinical Psychopharmacology 2006, 26: 595-599. PMID: 17110816, DOI: 10.1097/01.jcp.0000245558.14284.aa.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntipsychotic AgentsBehaviorBrainBrain MappingCluster AnalysisCross-Over StudiesDouble-Blind MethodFemaleFluorodeoxyglucose F18GlycineHumansInfusions, IntravenousMagnetic Resonance ImagingMaleNeuropsychological TestsPositron-Emission TomographyRadiopharmaceuticalsReference ValuesSerineConceptsN-methyl-D-aspartate receptor functionReceptor functionRegional cerebral metabolic rateAdministration of glycineCerebral metabolic effectsMagnetic resonance imaging studyPositron emission tomography studyHealthy control subjectsNMDA receptor functionCerebral metabolic rateEmission tomography studiesTest dayHealthy human subjectsResonance imaging studySignificant reductionPositron emission tomographyDorsolateral prefrontal cortexIntravenous glycinePlacebo infusionCerebral metabolismPatient populationControl subjectsGlycine administrationGlycine infusionIntravenous administration
2005
Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function
Krystal JH, Perry EB, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A, Cooper TB, MacDougall L, Abi-Saab W, D’Souza D. Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function. JAMA Psychiatry 2005, 62: 985-995. PMID: 16143730, DOI: 10.1001/archpsyc.62.9.985.Peer-Reviewed Original Research
2004
Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects
Krystal JH, Abi-Saab W, Perry E, D’Souza D, Liu N, Gueorguieva R, McDougall L, Hunsberger T, Belger A, Levine L, Breier A. Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology 2004, 179: 303-309. PMID: 15309376, DOI: 10.1007/s00213-004-1982-8.Peer-Reviewed Original ResearchConceptsGroup II metabotropic glutamate receptor agonistMetabotropic glutamate receptor agonistHealthy human subjectsNMDA glutamate receptor antagonistGlutamate receptor agonistsGlutamate receptor antagonistsTest dayCognitive effectsPerceptual changesKetamine infusionReceptor antagonistReceptor agonistDysphoric moodMemory impairmentBehavioral consequencesSignificant dose-related improvementGroup II mGluR agonistReceptor functionHuman subjectsMemoryNegative symptomsDose-related improvementNMDA receptor functionPreliminary evidenceDisruptive effects
2002
Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms
Abi-Saab W, Seibyl JP, D'Souza C, Karper LP, Gueorgueva R, Abi-Dargham A, Wong ML, Rajhans S, Erdos JP, Heninger GR, Charney DS, Krystal JH. Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms. Psychopharmacology 2002, 162: 55-62. PMID: 12107618, DOI: 10.1007/s00213-002-1057-7.Peer-Reviewed Original ResearchConceptsReceptor antagonismSchizophrenic patientsNeuroleptic-free schizophrenic patientsBrief Psychiatric Rating ScaleDouble-blind conditionsPsychiatric Rating ScaleTest dayRitanserin pretreatmentIntravenous infusionReceptor modulationAntipsychotic activityMale inpatientsReceptor stimulationPlasma prolactinCortisol levelsSchizoaffective disorderSchizophrenia symptomsPositive symptomsNegative symptomsRandomized orderPatientsRating ScaleBehavioral activationSymptomsRitanserin
2000
IV glycine and oral d-cycloserine effects on plasma and CSF amino acids in healthy humans
D’Souza D, Gil R, Cassello K, Morrissey K, Abi-Saab D, White J, Sturwold R, Bennett A, Karper L, Zuzarte E, Charney D, Krystal J. IV glycine and oral d-cycloserine effects on plasma and CSF amino acids in healthy humans. Biological Psychiatry 2000, 47: 450-462. PMID: 10704956, DOI: 10.1016/s0006-3223(99)00133-x.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAdministration, OralAdultAmino AcidsAntimetabolitesBiological AvailabilityCycloserineDose-Response Relationship, DrugDouble-Blind MethodFemaleGlycineHumansInjections, IntravenousMaleMiddle AgedNeuropsychological TestsPsychiatric Status Rating ScalesReceptors, GlycineReceptors, N-Methyl-D-AspartateReflex, StartleSerineConceptsAcoustic startle responseN-methyl-D-aspartate (NMDA) glutamate receptorsD-cycloserineStartle responseCentral nervous system effectsTest dayCSF glycine levelsOral D-cycloserineCSF amino acidsNervous system effectsDouble-blind conditionsCognitive test performanceD-cycloserine effectsHealthy human subjectsCentral bioavailabilityIntravenous glycineLumbar punctureSecond test dayGlycine administrationModulates neurotransmissionGlycine levelsGlutamate receptorsCoagonist siteCerebrospinal fluidHealthy humansDissociation of ketamine effects on rule acquisition and rule implementation: possible relevance to NMDA receptor contributions to executive cognitive functions
Krystal J, Bennett A, Abi-Saab D, Belger A, Karper L, D’Souza D, Lipschitz D, Abi-Dargham A, Charney D. Dissociation of ketamine effects on rule acquisition and rule implementation: possible relevance to NMDA receptor contributions to executive cognitive functions. Biological Psychiatry 2000, 47: 137-143. PMID: 10664830, PMCID: PMC10060085, DOI: 10.1016/s0006-3223(99)00097-9.Peer-Reviewed Original ResearchConceptsExecutive cognitive functionSecond test dayPerseverative errorsWCST performanceCognitive functionTest daySecond studyExecutive componentTask repetitionAltered perceptionWCSTNMDA antagonist ketamineNegative symptomsFrontal cortexRule acquisitionTest changesFirst studySingle repetitionKetamine effectsRepetitionTotal errorDistractibilityReceptor contributionNMDA receptor contributionRecall
1998
Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans
Krystal J, Karper L, Bennett A, D’Souza D, Abi-Dargham A, Morrissey K, Abi-Saab D, Bremner J, Bowers Jr. M, Suckow R, Stetson P, Heninger G, Charney D. Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans. Psychopharmacology 1998, 135: 213-229. PMID: 9498724, DOI: 10.1007/s002130050503.Peer-Reviewed Original ResearchConceptsWisconsin Card Sorting TestClinician-Administered Dissociative States ScalePerceptual alterationsAmnestic effectsInteractive effectsCard Sorting TestBrief Psychiatric Rating ScaleAttention impairmentSorting TestPerceptual effectsProverb interpretationEmotional distressDissociative effectsCortical impairmentNegative symptomsState scaleBehavioral effectsTest dayPsychiatric Rating ScaleLorazepam 2ImpairmentRating ScaleSubanesthetic ketamineHealthy humansPlacebo 2