2022
Exploratory 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 ResearchMeSH KeywordsAntidepressive AgentsDepressive Disorder, MajorHealthy VolunteersHumansN,N-DimethyltryptaminePilot ProjectsConceptsMajor 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 rate
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 alterations
2018
Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET
Radhakrishnan R, Nabulsi N, Gaiser E, Gallezot JD, Henry S, Planeta B, Lin SF, Ropchan J, Williams W, Morris E, D'Souza DC, Huang Y, Carson RE, Matuskey D. Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET. Journal Of Nuclear Medicine 2018, 59: 1445-1450. PMID: 29626125, PMCID: PMC6126437, DOI: 10.2967/jnumed.117.206516.Peer-Reviewed Original Research
2017
Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia
Hamilton HK, D'Souza DC, Ford JM, Roach BJ, Kort NS, Ahn KH, Bhakta S, Ranganathan M, Mathalon DH. Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia. Schizophrenia Research 2017, 191: 87-94. PMID: 28711472, PMCID: PMC5745273, DOI: 10.1016/j.schres.2017.06.040.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptor agonistAcetylcholine receptor agonistReceptor agonistHealthy volunteersN-methyl-D-aspartate receptor antagonistPathophysiology of schizophreniaAuditory processing abnormalitiesProfile of effectsMMN amplitudeNicotine preventsNicotine administrationReceptor hypofunctionNMDAR hypofunctionNMDAR antagonistsReceptor antagonistMismatch negativity (MMN) event-related potential (ERP) componentPresent doseNicotinic agonistsSchizophrenia patientsCigarette useKetamineDeviant typesNeurophysiological effectsSecondary analysisMMN abnormalitiesAttenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242
Ranganathan M, DeMartinis N, Huguenel B, Gaudreault F, Bednar MM, Shaffer CL, Gupta S, Cahill J, Sherif MA, Mancuso J, Zumpano L, D’Souza D. Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242. Molecular Psychiatry 2017, 22: 1633-1640. PMID: 28242871, DOI: 10.1038/mp.2017.6.Peer-Reviewed Original ResearchConceptsKetamine-induced impairmentVerbal learningAMPAR potentiatorsHopkins Verbal Learning TestN-methyl-D-aspartate receptorsVerbal Learning TestDissociative Symptoms ScaleKetamine-induced deficitsPsychotomimetic effectsMemory taskImmediate recallLearning TestCogState batteryMemory deficitsNegative Syndrome ScaleTreatment periodCognitive symptomsNMDAR functioningNMDAR antagonist ketamineNonhuman primatesNegative symptomsCognitive impairmentMemoryIsoxazolepropionic acid (AMPA) receptorsPathophysiology of schizophrenia
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 dayThe 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
2013
The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity
Driesen NR, McCarthy G, Bhagwagar Z, Bloch MH, Calhoun VD, D'Souza DC, Gueorguieva R, He G, Leung HC, Ramani R, Anticevic A, Suckow RF, Morgan PT, Krystal JH. The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity. Neuropsychopharmacology 2013, 38: 2613-2622. PMID: 23856634, PMCID: PMC3828532, DOI: 10.1038/npp.2013.170.Peer-Reviewed Original ResearchConceptsNMDA-RsRelationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans
Driesen NR, McCarthy G, Bhagwagar Z, Bloch M, Calhoun V, D'Souza DC, Gueorguieva R, He G, Ramachandran R, Suckow RF, Anticevic A, Morgan PT, Krystal JH. Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans. Molecular Psychiatry 2013, 18: 1199-1204. PMID: 23337947, PMCID: PMC3646075, DOI: 10.1038/mp.2012.194.Peer-Reviewed Original ResearchConceptsFunctional connectivityNegative symptomsGamma-aminobutyric acid (GABA) neuronsNMDA receptor antagonist ketamineAspartate glutamate receptor antagonistContinuous ketamine infusionGlutamate receptor antagonistsNMDA-R antagonistsCortical functional connectivityNMDA-R antagonist ketamineSchizophrenia-like symptomsHealthy human subjectsNegative Syndrome ScaleBrain functional connectivityPrimary samplesRegion-specific mannerFunctional magnetic resonanceKetamine infusionReceptor antagonistPathological increaseSyndrome ScaleSymptomsPreclinical researchKetamineBrain oscillations