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
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 1
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
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 dayDose-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 ResearchConceptsRecent 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 tasksNaltrexone 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
2008
Blunted 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
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 dataAnxietyNicotine effects on brain function and functional connectivity in schizophrenia
Jacobsen LK, D'Souza DC, Mencl WE, Pugh KR, Skudlarski P, Krystal JH. Nicotine effects on brain function and functional connectivity in schizophrenia. Biological Psychiatry 2004, 55: 850-858. PMID: 15050867, DOI: 10.1016/j.biopsych.2003.12.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceAttentionBrainBrain MappingBrief Psychiatric Rating ScaleCase-Control StudiesFemaleHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedNeuropsychological TestsNicotineNicotinic AgonistsReaction TimeRegression AnalysisSchizophreniaSmokeTask Performance and AnalysisVerbal LearningConceptsTask performanceFunctional connectivityFunctional magnetic resonance imaging (fMRI) scanningBrain regionsN-back taskMultiple cognitive domainsNetwork of regionsDifficult task conditionsAnterior cingulate cortexAttention loadMemory loadSelective attentionCognitive domainsTask conditionsCognitive functionCingulate cortexThalamocortical functional connectivityNicotine effectsCognitive dysfunctionBrain functionSchizophrenia patientsControl subjectsSchizophrenic subjectsMagnetic resonance imaging (MRI) scanningMental illness
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