{"rows":[{"id":3002,"title":"Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits.","normalized_title":"modeled long term effects of psilocybin on dynamic activity and effective connectivity of fronto striatal thalamic circuits","authors":"Pasquini L, Vohryzek J, Escrichs A, Perl YS, Ponce-Alvarez A, Idesis S, Girn M, Roseman L, Mitchell JM, Gazzaley A, Kringelbach M, Nutt DJ, Lyons T, Carhart-Harris RL, Deco G.","abstract":"Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we performed secondary analyses and applied computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first showed that dynamic FST activity increased 4 weeks after a full dose of psilocybin. We then proceeded to mechanistically account for these changes by providing tentative model-based support that reductions in the structure-function coupling contribute to increased dynamic FST activity postpsilocybin. Finally, we used computational approaches to show that psilocybin induces longitudinal increases in bottom-up and reduced top-down modulation of FST circuits. We then used publicly available receptor maps to show that cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, while increased information outflow via subcortical and limbic regions relates to local D2 receptor availability. Together, these findings suggest that increased FST flexibility weeks after a high dose of psilocybin is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism contributing to the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia nervosa.","journal":"Human Brain Mapping","publication_date":"2026-06-30","publication_year":2026,"doi":"10.1002/hbm.70596","pubmed_id":"42381187","source_url":"https://doi.org/10.1002/hbm.70596","keywords":"Thalamus, Corpus Striatum, Frontal Lobe, Nerve Net, Neural Pathways, Humans, Hallucinogens, Magnetic Resonance Imaging, Longitudinal Studies, Models, Neurological, Adult, Female, Male, Young Adult, Connectome, Psilocybin","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 11:03:06","last_checked":"2026-07-05 01:20:21","raw_json":"{\"europe_pmc_id\":\"42381187\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\",\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W7166854327\",\"openalex_url\":\"https://openalex.org/W7166854327\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":0,\"referenced_works\":[\"https://openalex.org/W1748789401\",\"https://openalex.org/W2026832357\",\"https://openalex.org/W2046230471\",\"https://openalex.org/W2058046532\",\"https://openalex.org/W2064319583\",\"https://openalex.org/W2116031726\",\"https://openalex.org/W2506717582\",\"https://openalex.org/W2525626228\",\"https://openalex.org/W2597410197\",\"https://openalex.org/W2608583841\",\"https://openalex.org/W2798279033\",\"https://openalex.org/W2893373014\",\"https://openalex.org/W2894570760\",\"https://openalex.org/W2911514809\",\"https://openalex.org/W2949457836\",\"https://openalex.org/W2969829800\",\"https://openalex.org/W3014803974\",\"https://openalex.org/W3015902292\",\"https://openalex.org/W3034488128\",\"https://openalex.org/W3084035636\",\"https://openalex.org/W3096208965\",\"https://openalex.org/W3118861474\",\"https://openalex.org/W3156937150\",\"https://openalex.org/W3175441262\",\"https://openalex.org/W3179473685\",\"https://openalex.org/W3185074371\",\"https://openalex.org/W3205085416\",\"https://openalex.org/W4200471428\",\"https://openalex.org/W4211211437\",\"https://openalex.org/W4213347163\",\"https://openalex.org/W4225144612\",\"https://openalex.org/W4243954785\",\"https://openalex.org/W4281774703\",\"https://openalex.org/W4292791729\",\"https://openalex.org/W4292937262\",\"https://openalex.org/W4302424620\",\"https://openalex.org/W4306408159\",\"https://openalex.org/W4308146982\",\"https://openalex.org/W4316016059\",\"https://openalex.org/W4321033185\",\"https://openalex.org/W4390227433\",\"https://openalex.org/W4409843587\"],\"authorships\":[{\"id\":\"https://openalex.org/A5018132997\",\"display_name\":\"Lorenzo Pasquini\",\"orcid\":\"https://orcid.org/0000-0002-7899-7061\"},{\"id\":\"https://openalex.org/A5073642716\",\"display_name\":\"Jakub Vohryzek\",\"orcid\":\"https://orcid.org/0000-0003-0994-5054\"},{\"id\":\"https://openalex.org/A5027614540\",\"display_name\":\"Anira Escrichs\",\"orcid\":\"https://orcid.org/0000-0002-6482-9737\"},{\"id\":\"https://openalex.org/A5091490801\",\"display_name\":\"Yonatan Sanz Perl\",\"orcid\":\"https://orcid.org/0000-0002-1270-5564\"},{\"id\":\"https://openalex.org/A5059409168\",\"display_name\":\"Adrián Ponce-Alvarez\",\"orcid\":\"https://orcid.org/0000-0003-1446-7392\"},{\"id\":\"https://openalex.org/A5135135782\",\"display_name\":\"Sebastian Idesis\",\"orcid\":\"https://orcid.org/0000-0002-8158-1673\"},{\"id\":\"https://openalex.org/A5017398137\",\"display_name\":\"Manesh Girn\",\"orcid\":\"https://orcid.org/0000-0003-0455-4273\"},{\"id\":\"https://openalex.org/A5139783089\",\"display_name\":\"Leor Roseman\",\"orcid\":null},{\"id\":\"https://openalex.org/A5078452831\",\"display_name\":\"Jennifer Mitchell\",\"orcid\":\"https://orcid.org/0000-0002-7567-8129\"},{\"id\":\"https://openalex.org/A5032146606\",\"display_name\":\"Adam Gazzaley\",\"orcid\":null},{\"id\":\"https://openalex.org/A5110937167\",\"display_name\":\"Morten Kringelbach\",\"orcid\":null},{\"id\":\"https://openalex.org/A5016082897\",\"display_name\":\"David Nutt\",\"orcid\":\"https://orcid.org/0000-0002-1286-1401\"},{\"id\":\"https://openalex.org/A5035033638\",\"display_name\":\"Taylor Lyons\",\"orcid\":\"https://orcid.org/0000-0002-3118-7344\"},{\"id\":\"https://openalex.org/A5139833133\",\"display_name\":\"Robin L. Carhart-Harris\",\"orcid\":null},{\"id\":\"https://openalex.org/A5047963275\",\"display_name\":\"Gustavo Deco\",\"orcid\":\"https://orcid.org/0000-0002-8995-7583\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S121666818\",\"source_display_name\":\"Human Brain Mapping\",\"landing_page_url\":\"https://doi.org/10.1002/hbm.70596\",\"is_oa\":true}}}","topic_tags":"Depression,Eating Disorders,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Healthy Volunteers","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W7166854327"},{"id":3023,"title":"Distinct brain responses to psilocybin and escitalopram in depression captured by the Fluctuation-Dissipation Theorem","normalized_title":"distinct brain responses to psilocybin and escitalopram in depression captured by the fluctuation dissipation theorem","authors":"Dagnino PC, Acero-Pousa I, Zamora-López G, Escrichs A, Erritzoe D, Nutt DJ, Carhart-Harris RL, Sanz Perl Y, Kringelbach ML, Deco G.","abstract":"In recent decades, the psychedelic psilocybin has been studied as a potential treatment for major depressive disorder (MDD), offering an alternative to traditional antidepressants. However, the brain changes underlying the clinical effects of different interventions remain unclear. Here, we investigated the effects of psilocybin and a conventional antidepressant, escitalopram, from the double-blind randomised controlled trial (DB-RCT) - NCT03429075 - on the brain’s hierarchical organisation. Using pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) we built whole-brain models and obtained a generative effective connectivity (GEC) matrix for each patient. Based on the GEC, we measured the level of non-equilibrium brain dynamics by quantifying the deviation from the fluctuation-dissipation theorem (FDT) and performed complementary analysis on brain segregation and asymmetry. Our results showed opposite reconfigurations of the hierarchical non-equilibrium brain dynamics following each treatment. Additionally, baseline measures effectively distinguished responders from non-responders within each treatment. These findings suggest that the deviation of the FDT may serve as a marker for differentiating the effects of psilocybin and escitalopram in MDD treatment, overall, contributing to the understanding of therapeutic mechanisms of depression.","journal":"bioRxiv","publication_date":"2026-06-15","publication_year":2026,"doi":"10.64898/2026.06.12.731811","pubmed_id":null,"source_url":"https://doi.org/10.64898/2026.06.12.731811","keywords":"","substance_tags":"psilocybin","source_name":"bioRxiv","date_added":"2026-07-01 11:03:45","last_checked":"2026-07-01 11:22:00","raw_json":"{\"europe_pmc_id\":\"PPR1253375\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Randomized Controlled Trial","study_type":"Randomized Controlled Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":119,"title":"Human brain changes after first psilocybin use.","normalized_title":"human brain changes after first psilocybin use","authors":"Lyons T, Spriggs M, Kerkelä L, Rosas FE, Roseman L, Mediano PAM, Timmermann C, Oestreich L, Pagni BA, Zeifman RJ, Hampshire A, Trender W, Douglass HM, Girn M, Godfrey K, Kettner H, Sharif F, Espasiano L, Gazzaley A, Wall MB, Erritzoe D, Nutt DJ, Carhart-Harris RL.","abstract":"Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes are detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being are seen at one-month. Diffusion tensor imaging (DTI) done before and one-month after 25 mg psilocybin reveals decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlate with decreases in brain network modularity (fMRI) over the same month. Enduring functional brain changes are largely absent, but network modularity change (numerical decrease) negatively correlates with well-being change (significant increase), in line with previous findings in depression. Increased cortical signal entropy (EEG) at 1- and 2-hours post-dosing predicts improved psychological well-being at one-month. Next-day psychological insight mediates the entropy to well-being relationship. All effects are exclusive to 25 mg psilocybin; no effects occur with a 1 mg psilocybin placebo.","journal":null,"publication_date":"2026-05-04","publication_year":2026,"doi":"10.1038/s41467-026-71962-3","pubmed_id":"42086570","source_url":"https://doi.org/10.1038/s41467-026-71962-3","keywords":"Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Electroencephalography, Adult, Female, Male, Young Adult, Diffusion Tensor Imaging, Psilocybin, Psychological Well-Being, Cognitive Flexibility","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-06-30 22:38:07","last_checked":"2026-07-01 11:22:00","raw_json":"{\"europe_pmc_id\":\"42086570\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Brain Imaging,Aging,Wellbeing","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":3216,"title":"Accurate and Interpretable Prediction of Antidepressant Treatment Response from Receptor-informed Neuroimaging","normalized_title":"accurate and interpretable prediction of antidepressant treatment response from receptor informed neuroimaging","authors":"Tolle HM, Luppi AI, Lawn T, Roseman L, Nutt D, Carhart-Harris RL, Mediano PAM.","abstract":"Conventional antidepressants show moderate efficacy in treating major depressive disorder. Psychedelic-assisted therapy holds promise, yet individual responses vary, underscoring the need for predictive tools to guide treatment selection. Here, we present graphTRIP (graph-based Treatment Response Interpretability and Prediction) - a geometric deep learning architecture that enables three advances: 1) accurate prediction of post-treatment depression severity using only pretreatment clinical and neuroimaging data; 2) identification of robust biomarkers; and 3) causal analysis of treatment effects and underlying mechanisms. Trained on data from a clinical trial comparing psilocybin and escitalopram ( NCT03429075 ), graphTRIP achieves strong predictive accuracy ( r = 0.72, p = 6.8 ×10 −8 ), and shows clear generalization to both an independent dataset and across brain atlases. The model identifies stronger functional connectivity within sensory networks as a robust predictor of poorer response across both treatments. In contrast, causal analysis implicates frontoparietal and default mode networks as key moderators of differential response, with stronger 5-HT1A- and 5-HT2A-related signalling in the frontoparietal network predicting escitalopram response but psilocybin resistance. Overall, this work advances precision medicine and biomarker discovery in depression.","journal":"bioRxiv","publication_date":"2025-07-02","publication_year":2025,"doi":"10.1101/2025.07.02.662710","pubmed_id":null,"source_url":"https://doi.org/10.1101/2025.07.02.662710","keywords":"","substance_tags":"psilocybin","source_name":"bioRxiv","date_added":"2026-07-01 11:03:48","last_checked":"2026-07-01 11:22:02","raw_json":"{\"europe_pmc_id\":\"PPR1046304\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Biomarkers,Aging,Clinical Trial","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":635,"title":"Exploring serotonergic psychedelics as a treatment for personality disorders.","normalized_title":"exploring serotonergic psychedelics as a treatment for personality disorders","authors":"Carrithers BM, Roberts DE, Weiss BM, King JD, Carhart-Harris RL, Gordon AR, Pagni BA, Moreau M, Ross S, Zeifman RJ","abstract":"Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy could hold potential for addressing core features of PDs through shared mechanisms of personality modulation. Although historical literature and observational studies suggest the potential clinical utility of psychedelics in treating PDs, rigorous research is lacking, and individuals with PDs are often excluded from modern psychedelic therapy trials. In the present review, we first discuss research on the effects of psychedelics in individuals with a PD through the conventional lens of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.; DSM-5-TR) categorical model. Next, using the dimensional DSM Alternative Model of Personality Disorders (DSM-AMPD) as a framework, we examine how psychedelics may affect self-functioning, interpersonal functioning, and pathological personality traits. We conclude by discussing the clinical relevance of psychedelic therapy as a treatment for personality pathology, including safety considerations, gaps and limitations, and recommendations for approaching psychedelic therapy within these more complex clinical populations.","journal":"Neuropharmacology","publication_date":"2025-06-30","publication_year":2025,"doi":"10.1016/j.neuropharm.2025.110413","pubmed_id":"40081794","source_url":"https://pubmed.ncbi.nlm.nih.gov/40081794/","keywords":"Personality disorders, Personality traits, Psilocybin-assisted therapy, Psychedelics, Psychopharmacology, Psychotherapy","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-07-01 06:48:04","last_checked":"2026-07-01 11:20:35","raw_json":"{\"pubmed_id\":\"40081794\"}","topic_tags":"Pharmacology,Mechanism of Action,Personality Change,Review Article,Observational Study,Safety","study_type":"Review Article","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":889,"title":"Human neuroimaging: fMRI.","normalized_title":"human neuroimaging fmri","authors":"Wall MB, Carhart-Harris RL.","abstract":"Human neuroimaging with functional Magnetic Resonance Imaging has been a key feature of the current wave of psychedelic research, in both healthy and clinical populations. The available data has suggested that classic psychedelics (psilocybin, LSD, DMT) have a characteristic effect of acutely and profoundly disrupting the normal pattern of resting-state connectivity in the human brain, and that this effect may be closely related to both the characteristic subjective phenomenology of psychedelics, and their more clinically-relevant longer-term effects on emotional brain systems. This chapter briefly outlines the basic methodological background of fMRI, and then provides an overview of the current state of knowledge of psychedelic drug action as revealed by task and resting-state fMRI, in both non-clinical and clinical cohorts. Current limitations of the field are largely addressable by ongoing and future work, particularly in terms of providing additional datasets, increased standardisation of data acquisition and analysis procedures, potential multi-modal imaging studies, and more open data-sharing. Neuroimaging with fMRI remains a central platform of modern psychedelic research, with implications for our mechanistic understanding of psychedelics, as well as a strong influence on the clinical development of psychedelic-based treatments.","journal":null,"publication_date":"2025-06-05","publication_year":2025,"doi":"10.1016/bs.irn.2025.04.013","pubmed_id":"40541308","source_url":"https://doi.org/10.1016/bs.irn.2025.04.013","keywords":"Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Neuroimaging","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 06:48:04","last_checked":"2026-07-01 11:22:03","raw_json":"{\"europe_pmc_id\":\"40541308\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Brain Imaging,Aging,Emotional Processing,Observational Study","study_type":"Observational Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":3108,"title":"Long-term effects of psilocybin on dynamic and effectivity connectivity of fronto-striatal-thalamic circuits","normalized_title":"long term effects of psilocybin on dynamic and effectivity connectivity of fronto striatal thalamic circuits","authors":"Pasquini L, Vohryzek J, Escrichs A, Sanz Perl Y, Ponce-Alvarez A, Idesis S, Girn M, Roseman L, Mitchell JM, Gazzaley A, Kringelbach M, Nutt DJ, Lyons T, Carhart-Harris RL, Deco G.","abstract":"Psilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we apply empirical methods and computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first show increases in FST dynamic activity four weeks after a full dose of psilocybin. We then proceed to mechanistically account for these increased dynamics, by showing that reduced structural constraints underlie increased FST dynamic activity post psilocybin. Further, we show that these reduced structural constraints come along with increased bottom-up and reduced top-down modulation of FST circuits. While cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, increased information outflow via subcortical and limbic regions relate to local D2 receptor availability. Together, these findings show that increased FST flexibility weeks after psilocybin administration is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism underling the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia. Significance Statement Fronto-striatal-thalamic systems, which underlie motivation and reward, go through profound functional and structural changes following psilocybin administration. We leveraged longitudinal fMRI data from a within-subject psilocybin trial in psychedelic-naïve healthy participants to show that psilocybin increases fronto-striatal-thalamic dynamic activity as well as flexibility four weeks after dosing. Computational modeling revealed that this increased flexibility is mechanistically caused by reduced structural constraints on functional dynamics. Further long-term changes included increased bottom-up and reduced top-down information flow mediated by the serotonergic and dopaminergic systems. This long-term functional re-organization of fronto-striatal-thalamic circuits may reflect a common mechanism underlying clinical symptoms improvements across diagnostic groups, such as increased openness, improved well-being, and reductions in anhedonia, apathy, and substance craving.","journal":"bioRxiv","publication_date":"2024-11-06","publication_year":2024,"doi":"10.1101/2024.11.06.622302","pubmed_id":null,"source_url":"https://doi.org/10.1101/2024.11.06.622302","keywords":"","substance_tags":"psilocybin","source_name":"bioRxiv","date_added":"2026-07-01 11:03:46","last_checked":"2026-07-01 11:22:01","raw_json":"{\"europe_pmc_id\":\"PPR936542\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Eating Disorders,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Wellbeing,Healthy Volunteers","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":1128,"title":"Time-resolved coupling between connectome harmonics and subjective experience under the psychedelic DMT","normalized_title":"time resolved coupling between connectome harmonics and subjective experience under the psychedelic dmt","authors":"Vohryzek J, Luppi A, Atasoy S, Deco G, Timmermann C, Carhart-Harris RL, Kringelbach ML.","abstract":"Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome, a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under DMT is reshaped in line with other reported psychedelic compounds; psilocybin, LSD and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics indexes the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.","journal":"bioRxiv","publication_date":"2024-05-30","publication_year":2024,"doi":"10.1101/2024.05.30.596410","pubmed_id":null,"source_url":"https://doi.org/10.1101/2024.05.30.596410","keywords":"","substance_tags":"psilocybin","source_name":"bioRxiv","date_added":"2026-07-01 06:48:05","last_checked":"2026-07-01 11:22:04","raw_json":"{\"europe_pmc_id\":\"PPR860621\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Mechanism of Action,Consciousness","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":3282,"title":"The Temporal Trajectory of the Psychedelic Mushroom Experience Mimics the Narrative Arc of the Hero’s Journey","normalized_title":"the temporal trajectory of the psychedelic mushroom experience mimics the narrative arc of the hero s journey","authors":"Brouwer A, Brown JK, Erowid E, Erowid F, Thyssen S, Raison CL, Carhart-Harris RL.","abstract":"Abstract Psychedelic therapy has the potential to become a revolutionary and transdiagnostic mental health treatment, yielding enduring benefits that are often attributed to the experiences that coincide with peak psychedelic effects. However, there may be an underrecognized temporal structure to this process that helps explain why psychedelic and related altered states of consciousness can have a initially distressing but ultimately a distress-resolving effect. Here we present a qualitative analysis of the self-reported ‘comeup’ or onset phase, and ‘comedown’ or falling phase, of the psychedelic experience. Focusing on psilocybin or psilocybin-containing mushrooms, we show that the comeup is more often characterized by negatively valenced feeling states, while the comedown phase is more often characterized by positively valenced feeling states of the sort often observed following recovery from illness or adversity. In this way, the temporal trajectory of the psychedelic experience could be seen to mimic the narrative arc of the monomythical ‘Hero’s Journey’.","journal":"Research Square","publication_date":"2024-02-22","publication_year":2024,"doi":"10.21203/rs.3.rs-3941205/v1","pubmed_id":null,"source_url":"https://doi.org/10.21203/rs.3.rs-3941205/v1","keywords":"","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 11:03:49","last_checked":"2026-07-01 11:22:03","raw_json":"{\"europe_pmc_id\":\"PPR810141\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}","topic_tags":"Consciousness,Clinical Trial","study_type":"Clinical Trial","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":1286,"title":"Psilocybin and Other Classic Psychedelics in Depression.","normalized_title":"psilocybin and other classic psychedelics in depression","authors":"Nutt DJ, Peill JM, Weiss B, Godfrey K, Carhart-Harris RL, Erritzoe D.","abstract":"Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences, insightful and emotional breakthroughs as well as mystical-type experiences. When coupled with psychological support, effects can produce a rapid improvement in mood among people with depression that can last for months. In this chapter, we summarise the scientific studies to date that explore the use of psychedelics in depressed individuals, highlighting key clinical, psychological and neuroimaging features of psychedelics that may account for their therapeutic effects. These include alterations in brain entropy that disrupt fixed negative ruminations, a period of post-treatment increased cognitive flexibility, and changes in self-referential psychological processes. Finally, we propose that the brain mechanisms underlying the therapeutic effect of serotonergic psychedelics might be distinct from those underlying classical serotonin reuptake-blocking antidepressants.","journal":null,"publication_date":"2023-12-31","publication_year":2023,"doi":"10.1007/7854_2023_451","pubmed_id":"37955822","source_url":"https://doi.org/10.1007/7854_2023_451","keywords":"Brain, Humans, Hallucinogens, Depression, Psilocybin","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 06:48:05","last_checked":"2026-07-01 11:22:01","raw_json":"{\"europe_pmc_id\":\"37955822\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Emotional Processing,Mystical Experience","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":3342,"title":"Statistical diversity distinguishes global states of consciousness","normalized_title":"statistical diversity distinguishes global states of consciousness","authors":"Starkey J, Carhart-Harris RL, Pigorini A, Nobili L, Barrett AB.","abstract":"Application of complexity measures to neurophysiological time series has seen increased use in recent years to identify neural correlates of global states of consciousness. Lempel-Ziv complexity is currently the de-facto complexity measure used in these investigations. However, by simply counting the number of patterns, this measure theoretically takes its maximum value for data that are completely random. Recently, a measure of ‘statistical complexity’ - which calculates the diversity of statistical interactions - has been devised which aims to account for and remove randomness seen in data. It was recently found that this measure decreases during anaesthesia in fruit flies. This paper investigates this statistical complexity measure on human neurophysiology data from different stages of sleep, and from individuals under the effects of three psychedelic substances: ketamine, lysergic acid diethylamide (LSD), and psilocybin. Results indicate that statistical complexity: (i) differentiates the different stages of sleep analogously to Lempel-Ziv complexity; (ii) increases relative to placebo for all three psychedelic substances. Thus, statistical complexity is a useful alternative measure for investigating the complexity of neural activity associated with different states of consciousness.","journal":"bioRxiv","publication_date":"2023-12-06","publication_year":2023,"doi":"10.1101/2023.12.05.570101","pubmed_id":null,"source_url":"https://doi.org/10.1101/2023.12.05.570101","keywords":"","substance_tags":"psilocybin","source_name":"bioRxiv","date_added":"2026-07-01 11:03:51","last_checked":"2026-07-01 11:22:05","raw_json":"{\"europe_pmc_id\":\"PPR770814\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Consciousness,Drug Interactions","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":3351,"title":"The entropic heart: Tracking the psychedelic state via heart rate dynamics","normalized_title":"the entropic heart tracking the psychedelic state via heart rate dynamics","authors":"Rosas FE, Mediano PA, Timmermann C, Luppi AI, Candia-Rivera D, Abbasi-Asl R, Gazzaley A, Kringelbach ML, Muthukumaraswamy S, Bor D, Garfinkel S, Carhart-Harris RL.","abstract":"A growing body of work shows that autonomic signals provide a privileged evidence-stream to capture various aspects of subjective and neural states. This work investigates the potential for autonomic markers to track the effects of psychedelics - potent psychoactive drugs with important scientific and clinical value. For this purpose, we introduce a novel Bayesian framework to estimate the entropy of heart rate dynamics under psychedelics. We also calculate Bayesian estimates of mean heart rate and heart rate variability, and investigate how these measures relate to subjective reports and neural effects. Results on datasets covering four drugs - lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), psilocybin, and sub-anaesthetic doses of the dissociative agent ketamine - show consistent increases in mean heart rate, high-frequency heart rate variability, and heart rate entropy during the psychedelic experience. Moreover, these effects have predictive power over various dimensions of the psychedelic experience. Changes in heart rate entropy were found to be correlated with increases in brain entropy, while other autonomic markers were not. Overall, our results show that a cost-efficient autonomic measure has the potential to reveal surprising detail about subjective and brain states, opening up a range of new research avenues to explore in both basic and clinical neuroscience.","journal":"bioRxiv","publication_date":"2023-11-08","publication_year":2023,"doi":"10.1101/2023.11.07.566008","pubmed_id":null,"source_url":"https://doi.org/10.1101/2023.11.07.566008","keywords":"","substance_tags":"psilocybin","source_name":"bioRxiv","date_added":"2026-07-01 11:03:51","last_checked":"2026-07-01 11:22:05","raw_json":"{\"europe_pmc_id\":\"PPR756922\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Biomarkers","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":1293,"title":"Personality Change in a Trial of Psilocybin Therapy vs Escitalopram Treatment for Depression - CORRIGENDUM.","normalized_title":"personality change in a trial of psilocybin therapy vs escitalopram treatment for depression corrigendum","authors":"Weiss B, Ginige I, Shannon L, Giribaldi B, Murphy-Beiner A, Murphy R, Baker-Jones M, Martell J, Nutt DJ, Carhart-Harris RL, Erritzoe D.","abstract":"","journal":null,"publication_date":"2023-07-18","publication_year":2023,"doi":"10.1017/s0033291723002039","pubmed_id":"37466289","source_url":"https://doi.org/10.1017/s0033291723002039","keywords":"Humans, Citalopram, Hallucinogens, Depression, Personality, Personality Disorders, Psilocybin, Escitalopram","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 06:48:05","last_checked":"2026-07-01 11:22:05","raw_json":"{\"europe_pmc_id\":\"37466289\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Personality Change","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":3153,"title":"Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression","normalized_title":"reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression","authors":"Wall MB, Demetriou L, Giribaldi B, Roseman L, Ertl N, Erritzoe D, Nutt DJ, Carhart-Harris RL.","abstract":"Psilocybin therapy is an emerging intervention for depression that may be at least as effective as standard first-line treatments i.e., Selective Serotonin Reuptake Inhibitors (SSRIs). Here we assess neural responses to emotional faces (fear, happy, and neutral) using Blood Oxygen-Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) in two groups with major depressive disorder: 1) a ‘psilocybin group’ that received two dosing sessions with 25mg plus six weeks of daily placebo, and 2) an ‘escitalopram group’ that received six weeks of the SSRI escitalopram, plus two dosing sessions with an inactive/placebo dose of 1mg psilocybin. Both groups had an equal amount of psychological support throughout. An emotional face fMRI paradigm was completed at baseline (pre-treatment) and at the six-week post-treatment primary endpoint (three weeks following psilocybin dosing sessions). An analysis examining the interaction between patient group (psilocybin vs. escitalopram) and time-point (pre-vs. post-treatment) showed a robust effect in a distributed network of cortical brain regions. Follow-up analyses showed that post-treatment BOLD responses to emotional faces of all types were significantly reduced in the escitalopram group, with no change, or even a slight increase, in the psilocybin group. Specific analyses of the amygdala showed a reduction of response to fear faces in the escitalopram group, but no effects for the psilocybin group. Despite large improvements in depressive symptoms in the psilocybin group, psilocybin-therapy had only a minor effect on brain responsiveness to emotional stimuli. We suggest that reduced emotional responsiveness may be a biomarker of SSRIs’ antidepressant action that is not shared by psilocybin-therapy.","journal":"medRxiv","publication_date":"2023-06-02","publication_year":2023,"doi":"10.1101/2023.05.29.23290667","pubmed_id":null,"source_url":"https://doi.org/10.1101/2023.05.29.23290667","keywords":"","substance_tags":"psilocybin","source_name":"medRxiv","date_added":"2026-07-01 11:03:47","last_checked":"2026-07-01 11:22:01","raw_json":"{\"europe_pmc_id\":\"PPR670172\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"medRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Brain Imaging,Receptor Pharmacology,Biomarkers,Aging,Emotional Processing,Drug Interactions","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":1487,"title":"Time-resolved network control analysis links reduced control energy under DMT with the serotonin 2a receptor, signal diversity, and subjective experience","normalized_title":"time resolved network control analysis links reduced control energy under dmt with the serotonin 2a receptor signal diversity and subjective experience","authors":"Singleton SP, Timmermann C, Luppi AI, Eckernäs E, Roseman L, Carhart-Harris RL, Kuceyeski A.","abstract":"Psychedelics offer a profound window into the functioning of the human brain and mind through their robust acute effects on perception, subjective experience, and brain activity patterns. In recent work using a receptor-informed network control theory framework, we demonstrated that the serotonergic psychedelics lysergic acid diethylamide (LSD) and psilocybin flatten the brain’s control energy landscape in a manner that covaries with more dynamic and entropic brain activity. Contrary to LSD and psilocybin, whose effects last for hours, the serotonergic psychedelic N,N-dimethyltryptamine (DMT) rapidly induces a profoundly immersive altered state of consciousness lasting less than 20 minutes, allowing for the entirety of the drug experience to be captured during a single resting-state fMRI scan. Using network control theory, which quantifies the amount of input necessary to drive transitions between functional brain states, we integrate brain structure and function to map the energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Consistent with previous work, we find that global control energy is reduced following injection with DMT compared to placebo. We additionally show longitudinal trajectories of global control energy correlate with longitudinal trajectories of EEG signal diversity (a measure of entropy) and subjective ratings of drug intensity. We interrogate these same relationships on a regional level and find that the spatial patterns of DMT’s effects on these metrics are correlated with serotonin 2a receptor density (obtained from separately acquired PET data). Using receptor distribution and pharmacokinetic information, we were able to successfully recapitulate the effects of DMT on global control energy trajectories, demonstrating a proof-of-concept for the use of control models in predicting pharmacological intervention effects on brain dynamics.","journal":"bioRxiv","publication_date":"2023-05-11","publication_year":2023,"doi":"10.1101/2023.05.11.540409","pubmed_id":null,"source_url":"https://doi.org/10.1101/2023.05.11.540409","keywords":"","substance_tags":"psilocybin","source_name":"bioRxiv","date_added":"2026-07-01 06:48:05","last_checked":"2026-07-01 11:22:04","raw_json":"{\"europe_pmc_id\":\"PPR659698\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Brain Imaging,Pharmacology,Receptor Pharmacology,Consciousness","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null},{"id":1528,"title":"Canalization and plasticity in psychopathology.","normalized_title":"canalization and plasticity in psychopathology","authors":"Carhart-Harris RL, Chandaria S, Erritzoe DE, Gazzaley A, Girn M, Kettner H, Mediano PAM, Nutt DJ, Rosas FE, Roseman L, Timmermann C, Weiss B, Zeifman RJ, Friston KJ.","abstract":"This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, we call 'canalization', which is close to Hebbian plasticity. These two forms of plasticity can be most easily distinguished by their relationship to 'precision' or inverse variance; TEMP relates to increased model variance or decreased precision, whereas the opposite is true for canalization. TEMP also subsumes increased learning rate, (Ising) temperature and entropy. Dictionary definitions of 'plasticity' describe it as the property of being easily shaped or molded; TEMP is the better match for this. Importantly, we propose that 'pathological' phenotypes develop via mechanisms of canalization or increased model precision, as a defensive response to adversity and associated distress or dysphoria. Our model states that canalization entrenches in psychopathology, narrowing the phenotypic state-space as the agent develops expertise in their pathology. We suggest that TEMP - combined with gently guiding psychological support - can counter canalization. We address questions of whether and when canalization is adaptive versus maladaptive, furnish our model with references to basic and human neuroscience, and offer concrete experiments and measures to test its main hypotheses and implications. This article is part of the Special Issue on \"National Institutes of Health Psilocybin Research Speaker Series\".","journal":null,"publication_date":"2022-12-26","publication_year":2022,"doi":"10.1016/j.neuropharm.2022.109398","pubmed_id":"36584883","source_url":"https://doi.org/10.1016/j.neuropharm.2022.109398","keywords":"Humans, Learning, Phenotype, United States, Major Depressive Disorder","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 06:48:05","last_checked":"2026-07-01 11:22:05","raw_json":"{\"europe_pmc_id\":\"36584883\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}","topic_tags":"Depression,Neuroplasticity,Mechanism of Action","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":1602,"title":"Body mass index (BMI) does not predict responses to psilocybin.","normalized_title":"body mass index bmi does not predict responses to psilocybin","authors":"Spriggs MJ, Giribaldi B, Lyons T, Rosas FE, Kärtner LS, Buchborn T, Douglass HM, Roseman L, Timmermann C, Erritzoe D, Nutt DJ, Carhart-Harris RL.","abstract":"BackgroundPsilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.MethodData were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.ResultsResults support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater 'dread of ego dissolution' in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.ConclusionsThese findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.","journal":"Journal of Psychopharmacology","publication_date":"2022-11-13","publication_year":2022,"doi":"10.1177/02698811221131994","pubmed_id":"36373934","source_url":"https://doi.org/10.1177/02698811221131994","keywords":"Humans, Serotonin, Hallucinogens, Body Mass Index, Bayes Theorem, Emotions, Psilocybin","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 06:48:05","last_checked":"2026-07-04 07:00:37","raw_json":"{\"europe_pmc_id\":\"36373934\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\",\"openalex_enrichment\":{\"openalex_id\":\"https://openalex.org/W4308952246\",\"openalex_url\":\"https://openalex.org/W4308952246\",\"openalex_relevance_score\":9,\"openalex_relevance_reasons\":[\"title:psilocybin\",\"abstract:psilocybin\",\"metadata:psilocybin\"],\"openalex_type\":\"article\",\"openalex_work_type\":null,\"cited_by_count\":15,\"referenced_works\":[\"https://openalex.org/W1966419092\",\"https://openalex.org/W1973927342\",\"https://openalex.org/W1978662219\",\"https://openalex.org/W1981740630\",\"https://openalex.org/W1985465524\",\"https://openalex.org/W1989324273\",\"https://openalex.org/W1993101534\",\"https://openalex.org/W1997058647\",\"https://openalex.org/W2001101493\",\"https://openalex.org/W2005441991\",\"https://openalex.org/W2009122980\",\"https://openalex.org/W2020220004\",\"https://openalex.org/W2025861780\",\"https://openalex.org/W2042593075\",\"https://openalex.org/W2052725640\",\"https://openalex.org/W2054831953\",\"https://openalex.org/W2075238613\",\"https://openalex.org/W2075969679\",\"https://openalex.org/W2078501925\",\"https://openalex.org/W2081861598\",\"https://openalex.org/W2084658093\",\"https://openalex.org/W2087193153\",\"https://openalex.org/W2104493382\",\"https://openalex.org/W2115308878\",\"https://openalex.org/W2118739111\",\"https://openalex.org/W2119738402\",\"https://openalex.org/W2123552131\",\"https://openalex.org/W2134099620\",\"https://openalex.org/W2161555895\",\"https://openalex.org/W2325134021\",\"https://openalex.org/W2396675581\",\"https://openalex.org/W2513336695\",\"https://openalex.org/W2552814605\",\"https://openalex.org/W2558412547\",\"https://openalex.org/W2559739670\",\"https://openalex.org/W2571392308\",\"https://openalex.org/W2600624779\",\"https://openalex.org/W2742569683\",\"https://openalex.org/W2788854095\",\"https://openalex.org/W2792444257\",\"https://openalex.org/W2807534705\",\"https://openalex.org/W2810374266\",\"https://openalex.org/W2894846833\",\"https://openalex.org/W2914255920\",\"https://openalex.org/W2962285119\",\"https://openalex.org/W3005218696\",\"https://openalex.org/W3015140823\",\"https://openalex.org/W3035524447\",\"https://openalex.org/W3083797211\",\"https://openalex.org/W3091936754\",\"https://openalex.org/W3097501343\",\"https://openalex.org/W3108632668\",\"https://openalex.org/W3112557491\",\"https://openalex.org/W3129221857\",\"https://openalex.org/W3135335789\",\"https://openalex.org/W3152417644\",\"https://openalex.org/W3156937150\",\"https://openalex.org/W3205506305\",\"https://openalex.org/W4211211437\",\"https://openalex.org/W4221001769\",\"https://openalex.org/W4230096730\",\"https://openalex.org/W4247665917\",\"https://openalex.org/W4390794773\"],\"authorships\":[{\"id\":\"https://openalex.org/A5025030452\",\"display_name\":\"Meg J. Spriggs\",\"orcid\":\"https://orcid.org/0000-0002-7800-1586\"},{\"id\":\"https://openalex.org/A5061472267\",\"display_name\":\"Bruna Giribaldi\",\"orcid\":null},{\"id\":\"https://openalex.org/A5035033638\",\"display_name\":\"Taylor Lyons\",\"orcid\":\"https://orcid.org/0000-0002-3118-7344\"},{\"id\":\"https://openalex.org/A5020498855\",\"display_name\":\"Fernando E. Rosas\",\"orcid\":\"https://orcid.org/0000-0001-7790-6183\"},{\"id\":\"https://openalex.org/A5044522468\",\"display_name\":\"Laura Kärtner\",\"orcid\":null},{\"id\":\"https://openalex.org/A5045797880\",\"display_name\":\"Tobias Buchborn\",\"orcid\":\"https://orcid.org/0000-0003-0538-5184\"},{\"id\":\"https://openalex.org/A5031966441\",\"display_name\":\"Hannah Douglass\",\"orcid\":\"https://orcid.org/0000-0002-4033-385X\"},{\"id\":\"https://openalex.org/A5020826324\",\"display_name\":\"Leor Roseman\",\"orcid\":\"https://orcid.org/0000-0001-9990-6029\"},{\"id\":\"https://openalex.org/A5055329548\",\"display_name\":\"Christopher Timmermann\",\"orcid\":\"https://orcid.org/0000-0002-2281-377X\"},{\"id\":\"https://openalex.org/A5044907549\",\"display_name\":\"David Erritzøe\",\"orcid\":\"https://orcid.org/0000-0002-7022-6211\"},{\"id\":\"https://openalex.org/A5101507504\",\"display_name\":\"David Nutt\",\"orcid\":\"https://orcid.org/0000-0002-6423-9411\"},{\"id\":\"https://openalex.org/A5072682798\",\"display_name\":\"Robin Carhart-Harris\",\"orcid\":\"https://orcid.org/0000-0002-6062-7150\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S136368880\",\"source_display_name\":\"Journal of Psychopharmacology\",\"landing_page_url\":\"https://doi.org/10.1177/02698811221131994\",\"is_oa\":true}}}","topic_tags":"Receptor Pharmacology,Wellbeing,Emotional Processing,Mystical Experience","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W4308952246"},{"id":1668,"title":"Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape.","normalized_title":"receptor informed network control theory links lsd and psilocybin to a flattening of the brain s control energy landscape","authors":"Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Nutt DJ, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski A.","abstract":"Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics.","journal":"Nature Communications","publication_date":"2022-10-02","publication_year":2022,"doi":"10.1038/s41467-022-33578-1","pubmed_id":"36192411","source_url":"https://doi.org/10.1038/s41467-022-33578-1","keywords":"Brain, Humans, Serotonin, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2A, Hallucinogens, Serotonin 5-HT2 Receptor Agonists, Psilocybin","substance_tags":"psilocybin","source_name":"Europe PMC","date_added":"2026-07-01 06:48:05","last_checked":"2026-07-04 07:00:37","raw_json":"{\"europe_pmc_id\":\"36192411\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe 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Parker Singleton\",\"orcid\":\"https://orcid.org/0000-0002-7102-7820\"},{\"id\":\"https://openalex.org/A5065968159\",\"display_name\":\"Andrea I. Luppi\",\"orcid\":\"https://orcid.org/0000-0002-3461-6431\"},{\"id\":\"https://openalex.org/A5038609897\",\"display_name\":\"Robin Carhart-Harris\",\"orcid\":null},{\"id\":\"https://openalex.org/A5074754048\",\"display_name\":\"Josephine Cruzat\",\"orcid\":\"https://orcid.org/0000-0002-3252-8657\"},{\"id\":\"https://openalex.org/A5020826324\",\"display_name\":\"Leor Roseman\",\"orcid\":\"https://orcid.org/0000-0001-9990-6029\"},{\"id\":\"https://openalex.org/A5016082897\",\"display_name\":\"David Nutt\",\"orcid\":\"https://orcid.org/0000-0002-1286-1401\"},{\"id\":\"https://openalex.org/A5047963275\",\"display_name\":\"Gustavo Deco\",\"orcid\":\"https://orcid.org/0000-0002-8995-7583\"},{\"id\":\"https://openalex.org/A5043559110\",\"display_name\":\"Morten L. Kringelbach\",\"orcid\":\"https://orcid.org/0000-0002-3908-6898\"},{\"id\":\"https://openalex.org/A5007542404\",\"display_name\":\"Emmanuel A. Stamatakis\",\"orcid\":\"https://orcid.org/0000-0001-6955-9601\"},{\"id\":\"https://openalex.org/A5031732445\",\"display_name\":\"Amy Kuceyeski\",\"orcid\":\"https://orcid.org/0000-0002-5050-8342\"}],\"primary_location\":{\"source_id\":\"https://openalex.org/S64187185\",\"source_display_name\":\"Nature Communications\",\"landing_page_url\":\"https://doi.org/10.1038/s41467-022-33578-1\",\"is_oa\":true}}}","topic_tags":"Brain Imaging,Receptor Pharmacology,Aging","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":"https://openalex.org/W4300960088"},{"id":1719,"title":"Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample.","normalized_title":"antidepressant effects of a psychedelic experience in a large prospective naturalistic sample","authors":"Nygart VA, Pommerencke LM, Haijen E, Kettner H, Kaelen M, Mortensen EL, Nutt DJ, Carhart-Harris RL, Erritzoe D","abstract":"Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were = 302, = 182, = 155 and = 109, respectively. Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.","journal":"Journal of psychopharmacology (Oxford, England)","publication_date":"2022-07-31","publication_year":2022,"doi":"10.1177/02698811221101061","pubmed_id":"35924888","source_url":"https://pubmed.ncbi.nlm.nih.gov/35924888/","keywords":"Psychedelics, anxiety, depression, mystical experience, psilocybin","substance_tags":"psilocybin","source_name":"PubMed","date_added":"2026-07-01 06:48:05","last_checked":"2026-07-01 11:20:38","raw_json":"{\"pubmed_id\":\"35924888\"}","topic_tags":"Depression,Anxiety,Emotional Processing,Mystical Experience,Observational Study","study_type":"Observational Study","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"published","openalex_id":null},{"id":3372,"title":"Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape","normalized_title":"mapping pharmacologically induced functional reorganisation onto the brain s neurotransmitter landscape","authors":"Luppi AI, Hansen JY, Adapa R, Carhart-Harris RL, Roseman L, Timmermann C, Golkowski D, Golkowski D, Ranft A, Ilg R, Jordan D, Bonhomme V, Vanhaudenhuyse A, Demertzi A, Jaquet O, Bahri MA, Alnagger NL, Cardone P, Peattie ARD, Manktelow AE, de Araujo DB, Sensi SL, Owen AM, Naci L, Menon DK, Misic B, Stamatakis EA.","abstract":"To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.","journal":"bioRxiv","publication_date":"2022-07-12","publication_year":2022,"doi":"10.1101/2022.07.12.499688","pubmed_id":null,"source_url":"https://doi.org/10.1101/2022.07.12.499688","keywords":"","substance_tags":"psilocybin","source_name":"bioRxiv","date_added":"2026-07-01 11:03:51","last_checked":"2026-07-01 11:22:05","raw_json":"{\"europe_pmc_id\":\"PPR518432\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}","topic_tags":"Receptor Pharmacology,Aging","study_type":"Other","hidden":0,"false_positive":0,"curation_notes":null,"merged_into_id":null,"curation_locked":0,"publication_status":"preprint","openalex_id":null}],"total":58,"page":1,"per_page":20,"pages":3,"resource":"papers","filters":{"q":null,"author":"Carhart-Harris RL.","substances":["psilocybin","psilocin"],"topic":null,"study_type":null,"cited_doi":null,"sources":[],"publication_statuses":[],"year":null,"journal":null,"from":null,"to":null,"sort":"newest","page":1,"per_page":"20"}}