2023
Preliminary 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
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
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 ResearchConceptsHuman 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 increaseSingle-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans
Hu Y, Ranganathan M, Shu C, Liang X, Ganesh S, Osafo-Addo A, Yan C, Zhang X, Aouizerat BE, Krystal JH, D’Souza D, Xu K. Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Scientific Reports 2020, 10: 3450. PMID: 32103029, PMCID: PMC7044203, DOI: 10.1038/s41598-020-59827-1.Peer-Reviewed Original ResearchConceptsSpecific genesCell type-specific genesGene expressionSingle-cell transcriptomic profilingCell typesGene expression correlationsAlters gene expressionTranscriptome mappingTranscriptomic profilingExpression correlationEnrichment analysisCommon genesImportant medical implicationsSignificant genesGenesMajor immune cell typesCell proliferationImmune cell typesImmune responseCell toxicityMedical implicationsCellsImportant insightsExpressionHuman immune cells
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 effortsEffects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis
Gupta S, De Aquino JP, D’Souza D, Ranganathan M. Effects of haloperidol on the delta-9-tetrahydrocannabinol response in humans: a responder analysis. Psychopharmacology 2019, 236: 2635-2640. PMID: 30919005, PMCID: PMC6697616, DOI: 10.1007/s00213-019-05235-x.Peer-Reviewed Original ResearchConceptsDissociative Symptoms ScalePANSS positive scalePsychotomimetic effectsHuman laboratory studiesRole of dopaminePsychosis-like effectsHaloperidol conditionNegative Syndrome ScalePANSS positive scoreDopaminergic antagonismPositive scalePlacebo conditionResponder analysisSyndrome ScaleSymptom ScaleDouble-blind studyEffects of haloperidolDopaminergic signalingOral haloperidolIndividualsOnly respondersPositive scoreIntravenous administrationHealthy individualsHaloperidol
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 1Cannabinoid 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
2017
Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information
Ranganathan M, Radhakrishnan R, Addy PH, Schnakenberg-Martin AM, Williams AH, Carbuto M, Elander J, Pittman B, Sewell R, Skosnik PD, D'Souza DC. Tetrahydrocannabinol (THC) impairs encoding but not retrieval of verbal information. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2017, 79: 176-183. PMID: 28642081, DOI: 10.1016/j.pnpbp.2017.06.019.Peer-Reviewed Original ResearchConceptsRey Auditory Verbal Learning TestVerbal informationInfluence of tetrahydrocannabinolVerbal Learning TestMemory-impairing effectsTotal immediate recallNon-verbal informationImpairs memory consolidationAdministration of tetrahydrocannabinolAcute memory impairmentPrincipal psychoactive constituentVerbal memoryImmediate recallIntravenous tetrahydrocannabinolLearning TestMemory consolidationComponent processesNeural synchronyMemory impairmentInformation processingUse of cannabisCannabis intoxicationRecallPsychoactive constituentEncoding
2015
Marijuana Legalization: Impact on Physicians and Public Health
Wilkinson ST, Yarnell S, Radhakrishnan R, Ball SA, D'Souza DC. Marijuana Legalization: Impact on Physicians and Public Health. Annual Review Of Medicine 2015, 67: 1-14. PMID: 26515984, PMCID: PMC4900958, DOI: 10.1146/annurev-med-050214-013454.BooksConceptsNausea/vomitingRobust clinical evidenceCertain public health issuesPublic health impactPublic health issuePublic healthHigh rateMarijuana useDependence/addictionLegitimate medical useNeuropathic painOpioid useClinical evidenceMultiple sclerosisPulmonary disordersUnintentional ingestionHealth problemsTherapeutic promiseAcute marijuana intoxicationHealth issuesMarijuana intoxicationRecreational useHealth impactsMarijuana productsCannabinoidsΔ9-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 taskTHCGABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC
Radhakrishnan R, Skosnik PD, Cortes-Briones J, Sewell RA, Carbuto M, Schnakenberg A, Cahill J, Bois F, Gunduz-Bruce H, Pittman B, Ranganathan M, D'Souza DC. GABA Deficits Enhance the Psychotomimetic Effects of Δ9-THC. Neuropsychopharmacology 2015, 40: 2047-2056. PMID: 25728472, PMCID: PMC4839528, DOI: 10.1038/npp.2015.58.Peer-Reviewed Original Research
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 daySmokersThe Effect of Chronic Cannabinoids on Broadband EEG Neural Oscillations in Humans
Skosnik PD, D'Souza DC, Steinmetz AB, Edwards CR, Vollmer JM, Hetrick WP, O'Donnell BF. The Effect of Chronic Cannabinoids on Broadband EEG Neural Oscillations in Humans. Neuropsychopharmacology 2012, 37: 2184-2193. PMID: 22713908, PMCID: PMC3422484, DOI: 10.1038/npp.2012.65.Peer-Reviewed Original ResearchConceptsNeural oscillationsAuditory steady-state responseCannabis usersCannabis groupGamma rangeChronic cannabis usersCentral cannabinoid-1 receptorsCognitive processesTransient ERPsChronic cannabisChronic cannabinoidsHz powerEEG dataCurrent studyEffects of cannabinoidsCannabisPsychopharmacological effectsExogenous cannabinoidsNaïve controlsElectroencephalographySpectral powerTrial powerEarly ageX frequencyERPCannabinoids, Working Memory, and Schizophrenia
Skosnik PD, Ranganathan M, D'Souza DC. Cannabinoids, Working Memory, and Schizophrenia. Biological Psychiatry 2012, 71: 662-663. PMID: 22449262, DOI: 10.1016/j.biopsych.2012.02.028.Peer-Reviewed Original ResearchDose-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