2025
The polypharmacology of psychedelics reveals multiple targets for potential therapeutics
Jain M, Gumpper R, Slocum S, Schmitz G, Madsen J, Tummino T, Suomivuori C, Huang X, Shub L, DiBerto J, Kim K, DeLeon C, Krumm B, Fay J, Keiser M, Hauser A, Dror R, Shoichet B, Gloriam D, Nichols D, Roth B. The polypharmacology of psychedelics reveals multiple targets for potential therapeutics. Neuron 2025 PMID: 40683247, DOI: 10.1016/j.neuron.2025.06.012.Peer-Reviewed Original ResearchPost-traumatic stress disorderAction of psychedelicsStress disorderPsychedelic effectsNeuropsychiatric conditionsSerotonin receptorsAcid diethylamidePsychedelicsDrug abuseCase of LSDG protein-coupled receptorsAdrenergic receptorsAction in vivoCluster headacheLSDClinical studiesPsilocybinSerotoninDopamineTherapeutic potentialAnxietyMescalineDiethylamideEfficacious actionDepressionNeurocognitive effects of psilocybin: A systematic and comprehensive review of neuroimaging studies in humans
Berkovitch L, Fauvel B, Preller K, Gaillard R. Neurocognitive effects of psilocybin: A systematic and comprehensive review of neuroimaging studies in humans. Neuroscience & Biobehavioral Reviews 2025, 175: 106239. PMID: 40456393, DOI: 10.1016/j.neubiorev.2025.106239.Peer-Reviewed Original ResearchConceptsEffects of psilocybinPsilocybin effectsNeuroimaging studiesBrain changesNeuroimaging techniquesTherapeutic effects of psilocybinTreat various psychiatric disordersFunctional brain changesSamples of healthy volunteersSerotonergic compoundsEmotional processingNeurobiological mechanismsMode networkPsychiatric disordersCognitive tasksPsychoactive effectsBrain activityNeuroimaging dataPsilocybinSelf-experienceAssociated with acute alterationsSocial functioningTherapeutic effectBrainNeuronal networksPsilocybin’s lasting action requires pyramidal cell types and 5-HT2A receptors
Shao L, Liao C, Davoudian P, Savalia N, Jiang Q, Wojtasiewicz C, Tan D, Nothnagel J, Liu R, Woodburn S, Bilash O, Kim H, Che A, Kwan A. Psilocybin’s lasting action requires pyramidal cell types and 5-HT2A receptors. Nature 2025, 642: 411-420. PMID: 40175553, PMCID: PMC12188471, DOI: 10.1038/s41586-025-08813-6.Peer-Reviewed Original ResearchConceptsMedial frontal cortexFrontal cortexMouse medial frontal cortexSingle dose of psilocybinDose of psilocybinImpact of psilocybinDensity of dendritic spinesPyramidal cell typesStress-related behaviorsDendritic spinesStress-related phenotypesCell-type-specific electrophysiologyPsilocybin effectsPT neuronsSerotonergic psychedelicsRemodeling of dendritic spinesCell typesElevated firing ratesPyramidal tractPsilocybinIT neuronsPsychedelicsStructural plasticityFiring rateCalcium transientsPsilocybin-assisted therapy for relapse prevention in alcohol use disorder: a phase 2 randomized clinical trial
Rieser N, Bitar R, Halm S, Rossgoderer C, Gubser L, Thévenaz M, Kreis Y, von Rotz R, Nordt C, Visentini M, Moujaes F, Engeli E, Ort A, Seifritz E, Vollenweider F, Herdener M, Preller K. Psilocybin-assisted therapy for relapse prevention in alcohol use disorder: a phase 2 randomized clinical trial. EClinicalMedicine 2025, 82: 103149. PMID: 40144690, PMCID: PMC11937691, DOI: 10.1016/j.eclinm.2025.103149.Peer-Reviewed Original ResearchAlcohol use disorderDose of psilocybinAlcohol use disorder patientsAlcohol useWithdrawal treatmentUse disorderOral doses of psilocybinTherapeutic effects of psilocybinSingle dose of psilocybinEffects of psilocybinInpatient withdrawal treatmentPsilocybin-assisted therapyDaily alcohol useReducing relapse ratesRelapse ratePsilocybin groupPsychotherapy sessionsReduce cravingFollow-upAbstinence durationRelapse preventionPlacebo groupPsilocybinPrevent relapsePsychotherapyA Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research
Yaden D, Graziosi M, Owen A, Agin-Liebes G, Aaronson S, Allen K, Barrett F, Bogenschutz M, Carhart-Harris R, Ching T, Cosimano M, Danforth A, Davis A, Garcia-Romeu A, Griffiths R, Grob C, Gründer G, Gukasyan N, Heinzerling K, Hendricks P, Holze F, Horton D, Johnson M, Kelmendi B, Peck S, Koslowski M, Liechti M, Mertens L, Moreno F, Nayak S, Nicholas C, Preller K, Rieser N, Ross S, Sergi K, Sloshower J, Smigielski L, Stenbæk D, Vollenweider F, Weiss B, Wolff M, Yaden M. A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research. Psychedelic Medicine 2025, 3: 1-18. PMID: 40351554, PMCID: PMC12060849, DOI: 10.1089/psymed.2024.0019.Peer-Reviewed Original ResearchResearch settingsSerotonin 2A receptor agonistAcute subjective effectsReflexive thematic analysisPsychological safetyPsychedelic treatmentIdentified themesSerotonergic psychedelicsSubjective effectsPsychological supportThematic analysisMedical staffPsychedelic experienceStates of consciousnessFamily historyPsilocybinReceptor agonistsWell-beingPsilocybin studiesDecades of researchPsychedelicsPsychoeducationPotential contraindicationsLevel of riskAnticipated outcomesClassification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression
Aboharb F, Davoudian P, Shao L, Liao C, Rzepka G, Wojtasiewicz C, Indajang J, Dibbs M, Rondeau J, Sherwood A, Kaye A, Kwan A. Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression. Nature Communications 2025, 16: 1590. PMID: 39939591, PMCID: PMC11822132, DOI: 10.1038/s41467-025-56850-6.Peer-Reviewed Original ResearchConceptsAcute fluoxetinePsychoactive drugsMarkers of neural plasticityImmediate early gene expressionC-fos expressionChronic fluoxetineNative brain tissueBehavioral effectsPsychedelic propertiesBrain regionsChance levelEarly gene expressionPsychoactive compoundsNeural plasticityFluoxetinePsilocybinMDMAMeasuring drug actionTested malesPsychedelicsPreclinical assaysDrug actionKetamineFemale miceDrug classification
2024
Psilocybin: From Psychiatric Pariah to Perceived Panacea
Fonzo G, Wolfgang A, Barksdale B, Krystal J, Carpenter L, Kraguljac N, Grzenda A, McDonald W, Widge A, Rodriguez C, Nemeroff C. Psilocybin: From Psychiatric Pariah to Perceived Panacea. American Journal Of Psychiatry 2024, 182: 54-78. PMID: 39741437, PMCID: PMC11694823, DOI: 10.1176/appi.ajp.20230682.Peer-Reviewed Original ResearchConceptsPsychiatric disordersTreatment of obsessive-compulsiveTreatment of psychiatric disordersTreatment of MDDSubstance use disordersEvidence-based treatmentsObsessive-CompulsiveDepressive disorderEvidence basePsychiatric treatmentExpectancy effectsRandomized Controlled TrialsPsilocybinPredictors of responseDiverse sampleMechanism of actionDisordersHead-to-head comparisonsEnglish-language articlesKnowledge of mechanisms of actionOpen-labelClinical responseDosing considerationsImproved blindingCancer diagnosisPsilocybin increases emotional empathy in patients with major depression
Jungwirth J, von Rotz R, Dziobek I, Vollenweider F, Preller K. Psilocybin increases emotional empathy in patients with major depression. Molecular Psychiatry 2024, 30: 2665-2672. PMID: 39695323, PMCID: PMC12092279, DOI: 10.1038/s41380-024-02875-0.Peer-Reviewed Original ResearchEmotional empathyDepressed patientsSocial cognitionMechanism of action of psychedelicsMultifaceted Empathy TestDose of psilocybinEnhance social cognitionPsilocybin-assisted therapyIncreased emotional empathyPotential of psychedelicsAction of psychedelicsPlacebo-controlled designEmpathy TestPsychological support interventionsPositive stimuliPsychiatric disordersTreating depressionClinical populationsPsychological mechanismsPsilocybinInterpersonal relationshipsSymptom improvementDepressionMental healthSubstance administrationThe revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges
Scala M, Fabbri C, Fusar-Poli P, Di Lorenzo G, Ferrara M, Amerio A, Fusar-Poli L, Pichiecchio A, Asteggiano C, Menchetti M, De Ronchi D, Sub-Project M, Fanelli G, Serretti A. The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges. CNS Spectrums 2024, 29: 570-584. PMID: 39655426, DOI: 10.1017/s1092852924002268.Peer-Reviewed Original ResearchAnxiety disordersPost-traumatic stress disorderPsychedelic-Assisted PsychotherapyObsessive-compulsive disorderSubstance use disordersPsychotic spectrumStandard antidepressantsResearch to clinical practiceTreating moodStress disorderAddictive behaviorsPsychopharmacological researchPsychiatric conditionsPsilocybinEvidence of efficacyAnxietyMethodological limitationsDisordersMoodMethodological constraintsMethodological rigorEvidence basePotential paradigm shiftLong-term efficacyCultural stigmaConsistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression
Høgsted E, Beliveau V, Ozenne B, Madsen M, Svarer C, Dam V, Johansen A, Fisher P, Knudsen G, Frokjaer V, Sankar A. Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression. The British Journal Of Psychiatry 2024, 226: 137-143. PMID: 39632615, DOI: 10.1192/bjp.2024.143.Peer-Reviewed Original ResearchFacets of neuroticismCortisol awakening responseHPA axis functionR bindingReduce neuroticismAxis functionPositron emission tomographyNEO Personality InventoryNEO-PI-RAssessment of neuroticismSerotonin 2A receptorMarkers of depressionTreatment of depressionPersonality InventoryMood symptomsAwakening responseNeuroticismPositive associationLatent variable modelsSelf-ConsciousnessDepressionReceptor bindingNovel interventionsPsilocybinFindings prompt considerationSynergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology
Shinozuka K, Jerotic K, Mediano P, Zhao A, Preller K, Carhart-Harris R, Kringelbach M. Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology. Translational Psychiatry 2024, 14: 485. PMID: 39632810, PMCID: PMC11618481, DOI: 10.1038/s41398-024-03187-1.Peer-Reviewed Original ResearchConceptsFunctional connectivityBetween-network functional connectivityLevels of analysisWithin-network FCBetween-drug differencesMeta-analysesD2 receptorsPsychedelic effectsSerotonergic psychedelicsNeuroimaging resultsNeuropsychiatric disordersStates of consciousnessPsychedelicsNeural fingerprintsAltered statesNeuroimagingPsilocybinHigh dosesLSDSignificantly higher ratesMolecular pharmacologySystematic reviewAddictionDepressionPhenomenologyPsilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats
Floris G, Dabrowski K, Zanda M, Daws S. Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats. Molecular Psychiatry 2024, 30: 1801-1816. PMID: 39433903, PMCID: PMC12015112, DOI: 10.1038/s41380-024-02788-y.Peer-Reviewed Original ResearchPrefrontal cortexHeroin seekingHeroin relapseDrug seekingSelf-AdministrationPrefrontal cortex of male ratsPrefrontal cortex of animalsCortex of male ratsHeroin self-administrationHeroin-seeking behaviorDrug-naive ratsOpioid-seeking behaviorSerotonin 2A receptorEfficacy of psilocybinAlcohol seekingHeroin takingForced abstinenceNucleus accumbensRelapse testRelapse behaviorIL-17AMaladaptive behaviorsPsychedelic compoundsAntagonist ketanserinPsilocybinPsilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors
Woodburn S, Levitt C, Koester A, Kwan A. Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors. ACS Chemical Neuroscience 2024, 15: 3034-3043. PMID: 39087917, PMCID: PMC12166970, DOI: 10.1021/acschemneuro.4c00279.Peer-Reviewed Original ResearchPost-traumatic stress disorderFear extinctionFear renewalExtinction retentionSerotonin receptorsPsilocybin effectsEffects of psilocybinExtinction-based therapiesProlonged exposure therapyFear conditioning paradigmAnalysis of sex differencesEnhanced fear extinctionFear learning paradigmAdministration of psilocybinConditioning paradigmExposure therapyFear learningStress disorderClassic psychedelicsPsilocybinSex differencesExtinction experimentsReceptor antagonismDrug effectsSerotoninT129 Prevalence of Psilocybin and Cannabis Concurrent Use During the COVID-19 Pandemic: An Analysis of the COVID-19 Cannabis Health Study
Vidot D, Baral A, Diggs B, Weerakoon S, Baquai M, Iyi R, Weiner M, Messiah S. T129 Prevalence of Psilocybin and Cannabis Concurrent Use During the COVID-19 Pandemic: An Analysis of the COVID-19 Cannabis Health Study. Drug And Alcohol Dependence 2024, 260: 110578. DOI: 10.1016/j.drugalcdep.2023.110578.Peer-Reviewed Original ResearchThe influence of psilocybin on subconscious and conscious emotional learning
Casanova A, Ort A, Smallridge J, Preller K, Seifritz E, Vollenweider F. The influence of psilocybin on subconscious and conscious emotional learning. IScience 2024, 27: 110034. PMID: 38883812, PMCID: PMC11177198, DOI: 10.1016/j.isci.2024.110034.Peer-Reviewed Original ResearchPsychedelic-Assisted PsychotherapyAgonist psilocybinFearful facesNeutral cuesEmotional cuesPsychiatric disordersSerotonergic psychedelicsSerotonin SignalingExploratory behaviorPsilocybinEmotional learningLearning effectCuesPlacebo groupPlaceboPsychotherapyLearning rateLearningPsychedelicsSerotoninReinforcement learningDisordersTreatment modalitiesBrainTaskContent analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms
Sakai K, Bradley E, Zamaria J, Agin-Liebes G, Kelley D, Fish A, Martini V, Ferris M, Morton E, Michalak E, O’Donovan A, Woolley J. Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms. Psychopharmacology 2024, 241: 1617-1630. PMID: 38687360, DOI: 10.1007/s00213-024-06585-x.Peer-Reviewed Original ResearchConceptsSerotonin reuptake inhibitorsReuptake inhibitorsPsilocybin mushroomsSSRI useSerotonergic psychedelic psilocybinMultiple neuropsychiatric disordersPsilocybin experiencePsychedelic psilocybinPsilocybin treatmentNeuropsychiatric disordersSSRIsPsilocybin researchSerotonin toxicityPsilocybinSerotoninProspective studyPsychological effectsCoadministrationDisordersSystematic searchEligible postsCurrent knowledgeInhibitorsTreatmentContent analysisPsychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial
Sloshower J, Zeifman R, Guss J, Krause R, Safi-Aghdam H, Pathania S, Pittman B, D’Souza D. Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial. Scientific Reports 2024, 14: 8833. PMID: 38632313, PMCID: PMC11024097, DOI: 10.1038/s41598-024-58318-x.Peer-Reviewed Original ResearchConceptsPsilocybin-assisted therapyPsychological flexibilityDepression severityModerate to severe MDDSpectrum of neuropsychiatric conditionsTarget psychological flexibilityIncrease psychological flexibilityMental health conditionsManualized psychotherapyPsilocybin treatmentSevere MDDDepressive disorderExperiential acceptanceCommitment TherapyDosing sessionsNeuropsychiatric conditionsPsychedelic trialsPlacebo-controlled trialWithin-subjectMDDPsilocybinAdministered placeboPlacebo-ControlledDepressionClinical samplesEfficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis
Yao Y, Guo D, Lu T, Liu F, Huang S, Diao M, Li S, Zhang X, Kosten T, Shi J, Bao Y, Lu L, Han Y. Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis. Psychiatry Research 2024, 335: 115886. PMID: 38574699, DOI: 10.1016/j.psychres.2024.115886.Peer-Reviewed Original ResearchConceptsMental disordersTreatment of mental disordersBorderline personality disorderObsessive-compulsive disorderTreat mood disordersSubstance-use disordersBody dysmorphic disorderPersonality disorderMood disordersDysmorphic disorderNegative moodEating DisordersLasting adverse effectsTobacco addictionPsychedelicsDisordersTreat symptomsPsilocybinSleep disordersAyahuascaTherapeutic effectMeta-analyzedLSDPTSDMDMASerotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile
Holze F, Singh N, Liechti M, D'Souza D. Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2024, 9: 472-489. PMID: 38301886, DOI: 10.1016/j.bpsc.2024.01.007.Peer-Reviewed Original ResearchConceptsSerotonergic psychedelicsSerotonin 2A receptor agonistPsychedelic effectsPsychedelic compoundsReceptor agonistsReview of efficacyPsychedelicsReceptor profilePsilocybinTherapeutic indicationsTherapeutic potentialPotential treatmentBinding profilesTherapeutic useClinical researchSerotonergicSerotoninPharmacokineticsMescalineDepressionEfficacyEffective durationAgonistsLSDResearchAssociations between behavioral and neuronal changes in self-referential processing following a single, moderate dose of psilocybin in depressed patients
Belinger L, Moujaes F, von Rotz R, Rieser N, Herdener M, Vollenweider F, Preller K. Associations between behavioral and neuronal changes in self-referential processing following a single, moderate dose of psilocybin in depressed patients. Neuroscience Applied 2024, 3: 104768. DOI: 10.1016/j.nsa.2024.104768.Peer-Reviewed Original Research
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply