2020
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
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 ResearchMeSH KeywordsAdultCannabinoid Receptor AgonistsDose-Response Relationship, DrugDronabinolFemaleHumansMalePsychoses, Substance-InducedRandomized Controlled Trials as TopicConceptsHuman 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
2018
The 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 1Dose-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
2015
Δ9-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
2014
Effects of Δ9-tetrahydrocannabinol in individuals with a familial vulnerability to alcoholism
Ranganathan M, Sewell RA, Carbuto M, Elander J, Schnakenberg A, Radhakrishnan R, Pittman B, D’Souza D. Effects of Δ9-tetrahydrocannabinol in individuals with a familial vulnerability to alcoholism. Psychopharmacology 2014, 231: 2385-2393. PMID: 24424782, DOI: 10.1007/s00213-013-3402-4.Peer-Reviewed Original ResearchConceptsPerceptual alterationsRewarding effectsSubjective effectsAlcohol-related behaviorsΔ9-THCExecutive functionEffects of alcoholSpatial memoryMemory impairmentCounterbalanced orderAlcohol problemsFamilial vulnerabilityCannabinoid receptor functionΔ9-tetrahydrocannabinolCannabinoid Δ9-tetrahydrocannabinolFirst human studyDouble-blind conditionsCB1R functionOutcome measuresIndividualsMemoryMeasuresAlcoholismSecondary outcome measuresHuman studies
2013
Pilot study of Intravenous Nicotine Effects on Cognitive Performance in Schizophrenia
Boggs DL, Ranganathan M, Sewell RA, Madonick S, D'Souza DC. Pilot study of Intravenous Nicotine Effects on Cognitive Performance in Schizophrenia. Schizophrenia Research 2013, 150: 323-324. PMID: 23953216, DOI: 10.1016/j.schres.2013.07.045.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAdolescentAdultAttentionCannabisCross-Over StudiesDose-Response Relationship, DrugDouble-Blind MethodDronabinolFemaleHumansMalePsychomotor PerformanceTime PerceptionYoung AdultConceptsCannabis 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 daySmokersDose-Related Behavioral, Subjective, Endocrine, and Psychophysiological Effects of the κ Opioid Agonist Salvinorin A in Humans
Ranganathan M, Schnakenberg A, Skosnik PD, Cohen BM, Pittman B, Sewell RA, D'Souza DC. Dose-Related Behavioral, Subjective, Endocrine, and Psychophysiological Effects of the κ Opioid Agonist Salvinorin A in Humans. Biological Psychiatry 2012, 72: 871-879. PMID: 22817868, PMCID: PMC3638802, DOI: 10.1016/j.biopsych.2012.06.012.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, InhalationAdultCardiovascular SystemCognitionCross-Over StudiesDiterpenes, ClerodaneDose-Response Relationship, DrugDrug MonitoringElectroencephalographyEuphoriaFemaleHallucinogensHumansHydrocortisoneIllicit DrugsMalePerceptionProlactinPsychiatric Status Rating ScalesPsychoses, Substance-InducedReceptors, Opioid, kappaSensationConceptsSA administrationSalvinorin APopular recreational drugElectroencephalogram spectral powerPrimary active ingredientPsychotomimetic effectsReceptor agonismOpiate receptorsEndocrine effectsHealthy subjectsSelective agonistHealthy individualsPerceptual alterationsPlasma cortisolEuphoric effectsCognitive deficitsRecreational drugsVital signsCounterbalanced studyEffect of SAYoung adultsAdverse effectsPsychophysiological effectsIndividual variabilityAdministrationDose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans
D'Souza DC, Fridberg DJ, Skosnik PD, Williams A, Roach B, Singh N, Carbuto M, Elander J, Schnakenberg A, Pittman B, Sewell RA, Ranganathan M, Mathalon D. Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans. Neuropsychopharmacology 2012, 37: 1632-1646. PMID: 22334121, PMCID: PMC3358754, DOI: 10.1038/npp.2012.8.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAttentionCerebral CortexCognitionCross-Over StudiesDose-Response Relationship, DrugDouble-Blind MethodDronabinolElectroencephalographyEvoked PotentialsHumansInfusions, IntravenousMaleReaction TimeConceptsRecent cannabis usersPerceptual alterationsERP componentsCannabis usersEvent-related potential taskSensory ERP componentsCannabis Use StatusModulation of eventsΔ9-THCProperties of cannabisContext updatingNeural correlatesP3b amplitudeTarget stimuliPsychophysiological indicesCortical processesP300b amplitudesProcessing speedCognitive deficitsPsychophysiological dataInformation processingAutomatic orientationCounterbalanced designSubjective effectsPotential tasks
2010
High dose D-serine in the treatment of schizophrenia
Kantrowitz JT, Malhotra AK, Cornblatt B, Silipo G, Balla A, Suckow RF, D'Souza C, Saksa J, Woods SW, Javitt DC. High dose D-serine in the treatment of schizophrenia. Schizophrenia Research 2010, 121: 125-130. PMID: 20541910, PMCID: PMC3111070, DOI: 10.1016/j.schres.2010.05.012.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnalysis of VarianceAntipsychotic AgentsChi-Square DistributionCognition DisordersDose-Response Relationship, DrugFemaleFollow-Up StudiesHumansMaleMiddle AgedNeuropsychological TestsPsychiatric Status Rating ScalesRegression AnalysisSchizophreniaSerineTreatment OutcomeYoung AdultConceptsD-serineBrain N-methyl-D-aspartate receptorsPlasma D-serine levelsN-methyl-D-aspartate receptorsSafety of dosesSignificant dose-dependent increaseDouble-blind investigationOpen-label trialDose-escalation studyDouble-blind studyLarge effect size improvementsTreatment of schizophreniaD-serine levelsPotential novel treatmentPharmacokinetics/pharmacodynamicsDose-dependent increaseNon-significant improvementEffect size improvementsMedication phasePersistent symptomsEscalation studyBrain levelsPlasma levelsPK analysisNeurocognitive dysfunction
2008
The effects of cannabinoids on serum cortisol and prolactin in humans
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J, D’Souza D. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology 2008, 203: 737. PMID: 19083209, PMCID: PMC2863108, DOI: 10.1007/s00213-008-1422-2.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultDose-Response Relationship, DrugDronabinolDrug ToleranceFemaleHallucinogensHumansHydrocortisoneInjections, IntravenousMaleMarijuana AbuseMiddle AgedProlactinConceptsPlasma prolactin levelsPlasma cortisol levelsProlactin levelsNeuroendocrine effectsCannabis exposureHealthy controlsNeuroendocrine functionHormonal levelsCortisol levelsFrequent usersChronic cannabis exposureHealthy control subjectsDose-related increaseEffects of cannabinoidsBaseline hormonal levelsDose-related effectsDevelopment of toleranceLimited dose-response dataDose-dependent mannerBlunted increaseMultiple dosesControl subjectsSerum cortisolHormone levelsPlasma cortisolBlunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent Users of Cannabis
D'Souza DC, Ranganathan M, Braley G, Gueorguieva R, Zimolo Z, Cooper T, Perry E, Krystal J. Blunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent Users of Cannabis. Neuropsychopharmacology 2008, 33: 2505-2516. PMID: 18185500, PMCID: PMC3799954, DOI: 10.1038/sj.npp.1301643.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmnesiaAttentionBrainDose-Response Relationship, DrugDouble-Blind MethodDronabinolDrug Administration ScheduleDrug ToleranceFemaleHallucinationsHallucinogensHumansHydrocortisoneMaleMarijuana AbuseMiddle AgedPerceptual DisordersProlactinPsychoses, Substance-InducedTachycardiaYoung AdultConceptsAmnestic effectsPerceptual alterationsDelta-9-TetrahydrocannabinolCannabis useSubjective effectsFrequent usersCannabisEffects of cannabinoidsIllicit substancesPsychotomimetic effectsEuphoric effectsHealthy controlsHealthy individualsMemoryImpairingPsychosisDose-related effectsIndividualsCortisolPsychotomimeticsAttentionPeopleUsersPlacebo-controlled studyEffect
2007
Absence of Significant Interactive Effects of High‐Dose d‐Cycloserine and Ethanol in Healthy Human Subjects: Preliminary Insights Into Ethanol Actions at the GlycineB Site of NMDA Glutamate Receptors
Trevisan L, Petrakis IL, Pittman B, Gueorguieva R, D’Souza D, Perry E, Limoncelli D, Krystal JH. Absence of Significant Interactive Effects of High‐Dose d‐Cycloserine and Ethanol in Healthy Human Subjects: Preliminary Insights Into Ethanol Actions at the GlycineB Site of NMDA Glutamate Receptors. Alcohol Clinical And Experimental Research 2007, 32: 36-42. PMID: 18028532, DOI: 10.1111/j.1530-0277.2007.00543.x.Peer-Reviewed Original ResearchConceptsCo-agonist siteHealthy human subjectsEthanol administrationD-cycloserineHigh-dose d-cycloserineAlcohol levelsReceptor functionPlacebo 4 hoursDouble-blind conditionsNMDA receptor functionNMDA glutamate receptorsMild sedative effectDoses of ethanolGlutamate receptor functionBreath alcohol levelsHuman subjectsVerbal fluencyGlycineB siteGroups of subjectsEthanol antagonismCombination of ethanolSedative effectsNMDA receptorsClinical significanceGlutamate receptorsPsychiatric safety of ketamine in psychopharmacology research
Perry EB, Cramer JA, Cho HS, Petrakis IL, Karper LP, Genovese A, O’Donnell E, Krystal JH, D’Souza D. Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacology 2007, 192: 253-260. PMID: 17458544, DOI: 10.1007/s00213-007-0706-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedClinical Trials as TopicDose-Response Relationship, DrugExcitatory Amino Acid AntagonistsFemaleHumansInfusions, IntravenousKetamineMaleMental DisordersMiddle AgedPsychopharmacologyRiskConceptsSubanesthetic dosesHealthy human subjectsKetamine administrationClinical research programHuman subjectsTest sessionsPsychotic spectrum disordersPsychiatric safetyResidual sequelaePlacebo infusionIntravenous infusionKetamine effectsPsychopharmacology studiesResultsFour hundredAdverse reactionsObjectiveTo reportHealthy subjectsStudy participationClinical investigationHealthy humansSide effectsKetamineInfusionDosesAdministration
2005
Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction
D’Souza D, Abi-Saab WM, Madonick S, Forselius-Bielen K, Doersch A, Braley G, Gueorguieva R, Cooper TB, Krystal JH. Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. Biological Psychiatry 2005, 57: 594-608. PMID: 15780846, DOI: 10.1016/j.biopsych.2004.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAkathisia, Drug-InducedArousalCognitionDose-Response Relationship, DrugDouble-Blind MethodDronabinolEndocrine SystemFemaleHumansInjections, IntravenousMaleMental RecallMiddle AgedMotor ActivityNeuropsychological TestsPerceptionPsychiatric Status Rating ScalesPsychotic DisordersPsychotropic DrugsSchizophreniaVerbal LearningConceptsSchizophrenia patientsAntipsychotic-treated schizophrenia patientsDelta-9-tetrahydrocannabinol effectsLong-term adverse eventsCognitive deficitsPlacebo-controlled studyDelta-9-THCTransient exacerbationAdverse eventsReceptor dysfunctionEndocrine effectsHealthy subjectsStudy participationPsychotic disordersPlasma prolactinSchizophrenia symptomsPatientsSchizophreniaCognitive effectsPerceptual alterationsDeficitsCannabisSubjectsAkathisiaExacerbation
2004
The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis
D'Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, Braley G, Gueorguieva R, Krystal JH. The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis. Neuropsychopharmacology 2004, 29: 1558-1572. PMID: 15173844, DOI: 10.1038/sj.npp.1300496.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnxietyArousalAttentionBehaviorCognitionDose-Response Relationship, DrugDouble-Blind MethodDronabinolFemaleHallucinogensHemodynamicsHumansHydrocortisoneInjections, IntravenousMaleMemory, Short-TermMental RecallPanicProlactinPsychiatric Status Rating ScalesPsychometricsPsychoses, Substance-InducedSpeechVerbal LearningConceptsCannabinoid receptor functionWord recallRecognition recallVerbal fluencyCognitive deficitsProspective safety dataNegative symptomsAbuse disordersHealthy individualsCounterbalanced studyMonths poststudyRecallPsychotomimetic effectsPsychotic disordersReceptor functionPsychosisEndogenous psychosesIndividualsDistractibilityFluencyTransient symptomsDisordersEndocrine effectsSafety dataAnxiety
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 humans