{ "meta": { "tracker_site_url": "https://psilocybin-research.com", "publication_tracker_url": "https://psilocybin-research.com/", "generated_at_utc": "2026-07-02 18:49:09", "record_count": 108 }, "papers": [ { "id": 3024, "title": "Sex-Specific Effects of Psilocybin Versus Escitalopram on Anxiety and Anhedonia: A Bayesian Reanalysis of Antidepressant Treatment Outcomes", "normalized_title": "sex specific effects of psilocybin versus escitalopram on anxiety and anhedonia a bayesian reanalysis of antidepressant treatment outcomes", "authors": "Frick A, Blest-Hopley G, Grin M, Erritzoe D, Nutt D, Carhart-Harris R.", "abstract": "Abstract Rationale: Major depressive disorder (MDD) shows marked sex differences in prevalence, symptomatology, and treatment response. However, women remain underrepresented in many clinical trials, and sex-specific treatment outcomes are rarely examined. Objectives This study reanalyzed data from a randomized controlled trial comparing psilocybin and escitalopram for MDD to evaluate sex differences across multiple psychological domains. Methods We reanalyzed data from a six-week, double-blind randomized controlled trial comparing psilocybin with escitalopram in adults with moderate-to-severe MDD. Post-treatment depressive symptoms (MADRS, QIDS-SR-16, BDI), anhedonia (SHAPS), anxiety (STAI), thought suppression (WBSI), and well-being (WEMWBS) were modeled as a function of sex, treatment condition, their interaction, and baseline symptom severity. Sexual dysfunction severity (PRSexDQ-SALSEX), assessed only at the six-week follow-up, was analyzed separately as an ordinal outcome. Results Sex-related patterns emerged for anxiety and anhedonia. Women receiving psilocybin showed greater reductions in anxiety than men (STAI: 95% CrI − 17.5 to − 3.29), whereas women receiving escitalopram showed greater reductions in anhedonia than men (SHAPS: 95% CrI − 4.63 to 0.00). For the remaining continuous outcomes, sex differences were generally small and uncertain. Sexual dysfunction severity was lower overall in the psilocybin group than in the escitalopram group and lower in women than in men, although the treatment-by-sex interaction was not significant. Conclusions This reanalysis identified domain-specific sex-related patterns in anxiety and anhedonia, suggesting that responses to psilocybin and escitalopram may differ between women and men. These preliminary findings support adequately powered, sex-balanced, and hormone-informed trials of serotonergic treatments for MDD.", "journal": "Research Square", "publication_date": "2026-06-18", "publication_year": 2026, "doi": "10.21203/rs.3.rs-9880403/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-9880403/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:45", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1255612\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Wellbeing,Clinical Trial,Randomized Controlled Trial,Drug Interactions", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "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" }, { "id": 3711, "title": "The entropic brain today.", "normalized_title": "the entropic brain today", "authors": "Carhart-Harris RL.", "abstract": "Introduced in 2014 and revised in 2018, the entropic brain hypothesis has accrued a wealth of supportive evidence. The hypothesis states that-along a dimension of the size of phenomenal consciousness-expansive states reliably exhibit increased brain entropy whereas the inverse applies for states of no or reduced consciousness. Examples of expansive states include expert meditation, flicker light stimulation, near-death-like experiences, atypical breathing, rapid-eye-movement sleep, the pre-ictal aura, unmedicated early psychosis and psychedelic drug states. Examples of states of no or reduced consciousness with low brain entropy, include disorders of consciousness, deep sleep, the anesthetized state, seizure, post-stroke, ageing, cognitive impairment, and neurodegenerative illness. It is shown that the entropic brain has convergent, correlative, predictive, discriminative and external validity. Regarding its predictive validity, increased brain entropy under psilocybin (in a supportive context) predicts subsequent improvements in mental health (improved wellbeing 1-month post-dose). Regarding its discriminative validity, changes in brain entropy selectively index the breadth of subjective experience versus alternative dimensions, such as arousal. Regarding portability/external validity, an entropy-related function is applied in generative artificial intelligence. In conclusion, the entropic brain is a useful model of conscious states.", "journal": null, "publication_date": "2026-06-09", "publication_year": 2026, "doi": "10.1093/brain/awag206", "pubmed_id": "42266156", "source_url": "https://doi.org/10.1093/brain/awag206", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:08:38", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"42266156\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Aging,Wellbeing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 62, "title": "Correction to: Preliminary Evidence of Sleep Improvements Following Psilocybin Administration, and their Involvement in Antidepressant Therapeutic Action.", "normalized_title": "correction to preliminary evidence of sleep improvements following psilocybin administration and their involvement in antidepressant therapeutic action", "authors": "Reid MJ, Kettner H, Blanken TF, Weiss B, Carhart-Harris R.", "abstract": "", "journal": null, "publication_date": "2026-06-04", "publication_year": 2026, "doi": "10.1007/s11920-026-01685-1", "pubmed_id": "42243392", "source_url": "https://doi.org/10.1007/s11920-026-01685-1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"42243392\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "General", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1946, "title": "Neural correlates of insight on psilocybin: a within-subjects, healthy volunteer study", "normalized_title": "neural correlates of insight on psilocybin a within subjects healthy volunteer study", "authors": "Pasquini Lorenzo, Girn Manesh, Kettner Hannes, Ostrand Avery, Allison Kate, Valtierra Christian, Lucas Will, McConnell Patrick, Miller Catriona, Griffith Sydney, Weinstein Dawn, Anderson Brian, Rosati Andrea, Mitchell Jennifer, Carhart-Harris Robin", "abstract": "", "journal": "JoCN Forum", "publication_date": "2026-05-07", "publication_year": 2026, "doi": "10.21428/8e6ba8ef.1db8272c", "pubmed_id": null, "source_url": "https://doi.org/10.21428/8e6ba8ef.1db8272c", "keywords": "", "substance_tags": "psilocybin", "source_name": "Crossref", "date_added": "2026-07-01 06:52:05", "last_checked": "2026-07-01 11:21:33", "raw_json": "{\"doi\":\"10.21428/8e6ba8ef.1db8272c\",\"reference_dois\":[],\"reference_count\":0}", "topic_tags": "Healthy Volunteers", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "id": 128, "title": "Effects of psychedelic use on authoritarian attitudes revisited.", "normalized_title": "effects of psychedelic use on authoritarian attitudes revisited", "authors": "Simonsson O, Lyons T, Marks J, Kettner H, Roseman L, Haijen E, Kaelen M, Carhart-Harris R.", "abstract": "BackgroundPrevious research suggests that psychedelics may, under certain conditions, decrease authoritarian attitudes, but larger and more rigorously designed studies are needed to confirm these findings.AimsWe aimed to examine the effects of psychedelic use on authoritarian attitudes.MethodsUsing data from three separate studies with different designs and populations, we investigated the relationship between psychedelic use and authoritarian attitudes. Study 1 was a naturalistic observational study with participants who planned to use psychedelics at their own initiative, Study 2 was a single-arm study with healthy volunteers who received psilocybin, and Study 3 was a randomized, controlled trial with patients diagnosed with depression who received psilocybin or escitalopram.ResultsAcross the three studies, results showed no significant changes in authoritarian attitudes after psychedelic use.ConclusionsContrary to previous research, the latest evidence is not compelling that psychedelic use influences authoritarian attitudes in a reliable direction. Future research should recruit larger and more diverse samples, collect additional context-related data, and also investigate political outcomes other than authoritarian attitudes.", "journal": null, "publication_date": "2026-05-01", "publication_year": 2026, "doi": "10.1177/02698811261443677", "pubmed_id": "42068187", "source_url": "https://doi.org/10.1177/02698811261443677", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"42068187\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Observational Study,Healthy Volunteers", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 2979, "title": "Observing the mind under psychedelics: conceptual metaphors used following four once-weekly macrodoses of psilocybin", "normalized_title": "observing the mind under psychedelics conceptual metaphors used following four once weekly macrodoses of psilocybin", "authors": "Rundquist Eric, Monasterio López Diego Nicolás, Oyarzo Alvarado Juan Jonathan, Carhart-Harris Robin, Pasquini Lorenzo, Vinson Erin, Girn Manesh, Ostrand Avery, Allison Kate, Kettner Hannes, Miller Catriona, Griffith Sydney, Gazzaley Adam, Rosati Andrea, Mitchell Jennifer", "abstract": "", "journal": "Philosophical Psychology", "publication_date": "2026-04-09", "publication_year": 2026, "doi": "10.1080/09515089.2026.2657452", "pubmed_id": null, "source_url": "https://doi.org/10.1080/09515089.2026.2657452", "keywords": "", "substance_tags": "psilocybin", "source_name": "Crossref", "date_added": "2026-07-01 06:55:42", "last_checked": "2026-07-01 11:21:33", "raw_json": "{\"doi\":\"10.1080/09515089.2026.2657452\",\"reference_dois\":[\"10.1234/ccd.2023.xxxxx\",\"10.4324/9780429058141-26\",\"10.4324/9781003300687\",\"10.1515/cogsem-2014-0012\",\"10.1016/j.neuropharm.2018.03.010\",\"10.1124/pr.118.017160\",\"10.3389/fnhum.2014.00020\",\"10.1016/j.tics.2018.11.002\",\"10.1162/netn_a_00250\",\"10.1515/revneuro-2018-0092\",\"10.1353/pbm.1976.0042\",\"10.1027/1016-9040.13.4.277\",\"10.1515/9780748629862\",\"10.1515/9781474405232\",\"10.1037/cns0000261\",\"10.1037/0003-066x.34.10.906\",\"10.1016/j.concog.2005.04.002\",\"10.1016/j.neuron.2006.05.001\",\"10.1016/j.socscimed.2023.116171\",\"10.1111/j.1468-0017.2006.00285.x\",\"10.1017/9781107762350\",\"10.1016/j.newideapsych.2024.101144\",\"10.1159/000467984\",\"10.1080/10926480709336752\",\"10.1075/dapsac.43\",\"10.1126/science.7384800\",\"10.2466/pms.1984.58.2.467\",\"10.1016/j.pharmthera.2018.11.010\",\"10.1556/2054.2023.00021\",\"10.1021/acsmedchemlett.0c00048\",\"10.1017/cbo9780511527715\",\"10.1177/096394700201100105\",\"10.1007/978-1-137-08545-0_18\",\"10.3389/fnhum.2014.00958\",\"10.7208/chicago/9780226470993.001.0001\",\"10.1093/med/9780198843122.001.0001\",\"10.1177/0022167820917767\",\"10.1101/2024.10.11.617955\",\"10.7551/mitpress/9780262019200.001.0001\",\"10.31234/osf.io/5ybhk_v1\",\"10.1101/2024.01.15.111268\",\"10.1177/02698811211066709\",\"10.1016/bs.alkal.2018.03.001\",\"10.1155/2014/307106\",\"10.1177/0963947020908622\",\"10.1515/jls-2020-2024\",\"10.1075/pc.24032.run\",\"10.1093/applin/amw028\",\"10.2307/jj.26931984.12\",\"10.19130/iifl.adel.4.2.2016.1400\",\"10.14198/elua.22349\",\"10.1007/s12144-021-01655-1\",\"10.1016/j.neubiorev.2023.105325\",\"10.1016/j.pragma.2022.12.011\",\"10.1073/pnas.2218949120\",\"10.1177/02698811211069113\"],\"reference_count\":76}", "topic_tags": "General", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 187, "title": "An international mega-analysis of psychedelic drug effects on brain circuit function.", "normalized_title": "an international mega analysis of psychedelic drug effects on brain circuit function", "authors": "Girn M, Doss MK, Roseman L, Preller KH, Palhano-Fontes F, Pasquini L, Barrett FS, Mallaroni P, Mason NL, Timmermann C, McCulloch DE, Fisher PM, Winston BS, Moujaes F, Muller F, Liechti ME, Vollenweider FX, Ramaekers JG, Kuypers K, Araujo DB, Sporns O, Siegel J, Dosenbach N, Nutt DJ, Carhart-Harris RL, Stamatakis EA, Bzdok D.", "abstract": "Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and a Bayesian hierarchical modeling framework, we discovered several common features in the induced alterations to brain function across drugs and sites. Most prominently, we identified a core signature of increased functional connectivity between transmodal (default, frontoparietal and limbic) and unimodal networks (visual and somatomotor), with subnetwork specificity. Furthermore, key subcortical regions (thalamus, caudate and putamen) and the cerebellum exhibited altered coupling with sensorimotor networks. In contrast to several single-site reports, Bayesian modeling revealed weak-to-moderate and selective reductions in within-network functional connectivity, with substantial variability across drugs and networks. Together, these findings extend past work by demonstrating that psychedelics reconfigure large-scale cortical organization while selectively engaging subcortical circuitry. This study provides the most comprehensive synthesis of psychedelic brain action to date, helping resolve inconsistencies and offering a probabilistic map of how psychedelics alter large-scale brain organization. We hereby provide a cornerstone to benchmark and shepherd future psychedelic neuroimaging research.", "journal": null, "publication_date": "2026-04-05", "publication_year": 2026, "doi": "10.1038/s41591-026-04287-9", "pubmed_id": "41942645", "source_url": "https://doi.org/10.1038/s41591-026-04287-9", "keywords": "Brain, Nerve Net, Humans, Banisteriopsis, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Bayes Theorem, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"41942645\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Mechanism of Action,Aging", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 4, "title": "The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis.", "normalized_title": "the role of therapeutic alliance in psilocybin treatment for treatment resistant depression a post hoc path analysis", "authors": "Goodwin GM, Aaronson ST, Alvarez O, Carhart-Harris R, Croal M, Feifel D, Hellerstein DJ, Husain MI, Kelly JR, Kirlic N, Licht RW, Marwood L, Nowakowska A, Páleníček T, Repantis D, Schoevers RA, Simmons H, Soares JC, Somers M, Tsai J, Wahba M, Williams E, Young AH, Young MB, Zisook S, Malievskaia E.", "abstract": "IntroductionThe contribution of patient support to psilocybin's antidepressant effects remains uncertain.MethodsRelationships between therapeutic alliance (Scale to Assess Therapeutic Relationship-Patient version; STAR-P), psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire and Emotional Breakthrough Inventory; 5D-ASC and EBI) and clinical outcomes (Montgomery-Åsberg Depression Rating Scale; MADRS) were explored using correlation and path analysis for individuals with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support (N = 79).ResultsChange from Baseline to Week 3 MADRS scores showed weaker correlations with pre-dosing therapeutic alliance (-0.178) than with measures of the psychedelic experience: EBI (-0.637), Oceanic Boundlessness (-0.508), and Visual Restructuralization (-0.516). Path analysis showed no nominally significant direct effects of therapeutic alliance on Week 3 MADRS scores, but there were nominally significant effects of therapeutic alliance on psychedelic experience (Oceanic Boundlessness (β = 0.28), Visual Restructuralization (β = 0.27), and Auditory Alterations (β = 0.25)). Only one indirect effect of therapeutic alliance on clinical outcome reached nominal significance (via Visual Restructuralization; β = -0.15). Stronger effects were seen on clinical outcomes for psychedelic experience (EBI (β = -0.59), Oceanic Boundlessness (β = -0.53), Visual Restructuralization (β = -0.54), and Auditory Alterations (β = -0.24)).ConclusionsThe therapeutic alliance appeared to facilitate the psychedelic experience, and these experiences in turn had stronger nominally significant direct effects on clinical outcomes. The effects of the alliance itself on therapeutic efficacy were either limited or absent.Trial registrationEudraCT number: 2017-003288-36; Clinicaltrials.gov identifier: NCT03775200.", "journal": null, "publication_date": "2026-03-22", "publication_year": 2026, "doi": "10.1016/j.jad.2026.121662", "pubmed_id": "41881122", "source_url": "https://doi.org/10.1016/j.jad.2026.121662", "keywords": "Humans, Hallucinogens, Treatment Outcome, Psychiatric Status Rating Scales, Adult, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Therapeutic Alliance", "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\":\"41881122\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Consciousness,Emotional Processing,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 237, "title": "The combination of exercise and psychedelics for the treatment of major depressive disorder.", "normalized_title": "the combination of exercise and psychedelics for the treatment of major depressive disorder", "authors": "Fabiano N, Stubbs B, Lawrence DW, Rosenblat JD, Teixeira PJ, Wong S, Zhou C, Carhart-Harris R", "abstract": "Upwards of 50% of people do not respond to the primary treatment modalities for major depressive disorder (MDD), which has led to increased attention and use of alternative methods, including exercise and psychedelics. While interventions using either exercise or psychedelics have demonstrated largely positive results in isolation, their synergistic potential has yet to be explored. As such, this commentary provides an overview of exercise/psychedelics as a treatment for depression and their potential synergy and/or complementarity. From a biological perspective, psychedelics acutely enhance brain-derived neurotrophic factor (BDNF) signalling, while exercise provides sustained BDNF elevation; psychedelics enhance neuroplasticity largely in the cortex (with only modest effects in the hippocampus), while exercise boosts hippocampal neurogenesis; psychedelics increase glutamate release via stimulation of 5-HT receptors on pyramidal neurons, while exercise enhances glutamatergic transmission via the endocannabinoid system and reduction of systemic inflammation; both boost serotonin release; and psychedelics temporarily disrupt functional connectivity between the hippocampus and default mode network (DMN), while exercise normalizes this connectivity, which may sustain post-psychedelic gains. Through the lens of psychological and behaviour change, psychedelics appear to facilitate the adoption or maintenance of physical activity habits, increase psychological flexibility, and since exercise is associated with emotional resilience to acute stress, this may allow users to experience deeper immersion and exploration during their psychedelic experience, improving antidepressant outcomes. In summary, exercise and psychedelics have numerous potential complementary mechanisms, therefore, future research is warranted to explore the efficacy, tolerability, safety, and neurobiology of this combination.", "journal": "Discover mental health", "publication_date": "2026-03-06", "publication_year": 2026, "doi": "10.1007/s44192-026-00408-5", "pubmed_id": "41793582", "source_url": "https://pubmed.ncbi.nlm.nih.gov/41793582/", "keywords": "Exercise, Depression, Major depressive disorder, Physical activity, Psilocybin, Psychedelic", "substance_tags": "psilocybin", "source_name": "PubMed", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-01 11:20:34", "raw_json": "{\"pubmed_id\":\"41793582\"}", "topic_tags": "Depression,Neuroplasticity,Neurogenesis,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Resilience,Emotional Processing,Psychological Flexibility,Safety,Inflammation", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3254, "title": "The entropic brain today", "normalized_title": "the entropic brain today", "authors": "Carhart-Harris R.", "abstract": "Introduced in 2014 and revised in 2018, the entropic brain hypothesis has accrued a wealth of supportive evidence. The hypothesis states that- along a dimension of breadth of conscious experience- ‘expansive states’ reliably exhibit increased brain entropy whereas the inverse applies for states of no or reduced consciousness. Examples of expansive states include those of expert meditation, flicker light stimulation, the near-death experience, atypical breathing, rapid-eye-movement sleep, the pre-ictal aura, unmedicated early psychosis and psychedelic drug states. Example states of no or reduced consciousness with low brain entropy, include disorders of consciousness, deep sleep, the anesthetized state, seizure, post-stroke, ageing, cognitive impairment, and neurodegenerative disorders. It is shown here that the entropic brain has convergent, correlative, predictive, discriminative and external validity. Regarding its predictive validity, increased brain entropy under psilocybin predicts subsequent improvements in mental health (improved well-being 1-month post-dose). Regarding its discriminative validity, changes in brain entropy selectively index the breadth of subjective experience versus alternative dimensions, such as arousal. Regarding portability/external validity, an entropy (temperature) function is used in generative artificial intelligence. In conclusion, the entropic brain is proving to be a useful model of conscious states.", "journal": "PsyArXiv", "publication_date": "2025-12-11", "publication_year": 2025, "doi": "10.31234/osf.io/ubzq3_v1", "pubmed_id": null, "source_url": "https://doi.org/10.31234/osf.io/ubzq3_v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "PsyArXiv", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR1133707\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"PsyArXiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Aging,Wellbeing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3754, "title": "Defining ‘psychedelic’", "normalized_title": "defining psychedelic", "authors": "Ostrand A, Nour M, Timmermann C, Rosati A, Luan LX, Gómez-Emilsson A, Bornemann J, Greenway K, Roseman L, Carhart-Harris R.", "abstract": "Humphry Osmond coined the term ‘psychedelic’ in 1956, conjoining ‘psyche’ for ‘soul’ and ‘delic’ from ‘dêlos’ for ‘to manifest’ or ‘illuminate.’ Soul-illumination is an adjective that describes a psychological state or process. However, Osmond’s intention was to use the adjective to name- not just a state- but a category of drug that can induce the subjective effect as its principal action; thus, when used in this way, psychedelic becomes a ‘nominalized adjective;’ describing a ‘thing’ (i.e., a drug) that can induce the described state. Consistent with the etymology of psychedelic, the present work is guided by phenomenology, recognizing its fundamental ontology. Accordingly, we examine the main subjective effect of three different psychoactive drugs, psilocybin, ketamine, and MDMA (variable label, Drug). Over two-hundred participants rated Delphi-derived subjective rating scale items based on their personal experiences with all three drugs. Factor analyses revealed 3 or 4 sufficiently independent dimensions of subjective experience (variable label, Effects). A machine learning classifier successfully predicted Drug from Effects, validating the hypothesis that psilocybin, ketamine and MDMA are categorically distinct as determined by their differential ability to induce the following Effects: 1) visions and psychological insight (psilocybin), 2) dissociation (ketamine) and 3) pro-social feelings, epitomized by feelings of love (MDMA). We conclude that psilocybin is an exemplar psychedelic drug- a category of drug definable by the induction of a psychedelic state- the quintessential psychedelic phenomenon. This state is characterized by visions and psychological insight.", "journal": "PsyArXiv", "publication_date": "2025-12-03", "publication_year": 2025, "doi": "10.31234/osf.io/5ybhk_v1", "pubmed_id": null, "source_url": "https://doi.org/10.31234/osf.io/5ybhk_v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "PsyArXiv", "date_added": "2026-07-01 11:10:19", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR1130688\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"PsyArXiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "General", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 413, "title": "Correction: Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin.", "normalized_title": "correction short and long term modulation of rat prefrontal cortical activity following single doses of psilocybin", "authors": "Purple RJ, Gupta R, Thomas CW, Golden CT, Palomero-Gallagher N, Carhart-Harris R, Froudist-Walsh S, Jones MW.", "abstract": "", "journal": null, "publication_date": "2025-11-30", "publication_year": 2025, "doi": "10.1038/s41380-025-03231-6", "pubmed_id": "40913115", "source_url": "https://doi.org/10.1038/s41380-025-03231-6", "keywords": "", "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\":\"40913115\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Animal Study", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 299, "title": "A Virtual Clinical Trial of Psychedelics to Treat Patients With Disorders of Consciousness.", "normalized_title": "a virtual clinical trial of psychedelics to treat patients with disorders of consciousness", "authors": "Alnagger NLN, Cardone P, Martial C, Perl YS, Mindlin I, Sitt JD, Roseman L, Carhart-Harris R, Nutt D, Mallaroni P, Mason N, Ramaekers JG, Bonhomme V, Laureys S, Deco G, Gosseries O, Núñez P, Annen J.", "abstract": "Disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have limited treatment options and are characterized by low complexity of brain activity. Recent research suggests that psychedelic drugs, which enhance the complexity of brain activity, could offer promising therapies. Here, individualized whole-brain computational models are developed for patients with DoC, optimized with empirical functional magnetic resonance imaging data and diffusion-weighted imaging data, upon which the administration of lysergic acid diethylamide (LSD) and psilocybin is simulated. An in silico perturbation protocol is applied to assess brain dynamics, first distinguishing between different states of consciousness, including DoC, anesthesia, and the psychedelic state. Then, brain dynamics are assessed before and after a simulation of psychedelic drugs on patients with DoC. Findings indicated that the simulation of LSD and psilocybin shifted the brain activity of patients with DoC closer to criticality (the point at a phase transition between order and chaos), with a greater effect in patients in the MCS. In patients with UWS, the treatment response correlated with structural connectivity, while in patients in the MCS, it aligned with baseline functional connectivity. These results offer a computational foundation for using psychedelics in DoC treatment and highlight the potential future role of computational modeling in drug discovery and personalized medicine.", "journal": null, "publication_date": "2025-11-19", "publication_year": 2025, "doi": "10.1002/advs.202511780", "pubmed_id": "41261994", "source_url": "https://doi.org/10.1002/advs.202511780", "keywords": "Brain, Humans, Consciousness Disorders, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Computer Simulation, Adult, Female, Male, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"41261994\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Consciousness,Aging,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 436, "title": "Negative affective bias in depression following treatment with psilocybin or escitalopram - a secondary analysis from a randomized trial.", "normalized_title": "negative affective bias in depression following treatment with psilocybin or escitalopram a secondary analysis from a randomized trial", "authors": "Martens MAG, Cunha BG, Erritzoe D, Nutt D, Carhart-Harris R, Harmer CJ.", "abstract": "Recent clinical trial data suggests that ratings on depression scales are lowered after psilocybin therapy compared to placebo, though it is unclear what neuropsychological mechanisms underpin these effects. This study compared psilocybin, with an established antidepressant, escitalopram, to investigate whether there are shared or distinct effects on emotional information processing. Patients with long-standing moderate-to-severe depression were randomly and double-blindly assigned in a 1:1 ratio to receive either 1) two doses of 25 mg of psilocybin, 3-weeks apart, plus 6-weeks of daily placebo (psilocybin group N = 30); or 2) two doses of 1 mg of psilocybin 3-weeks apart plus 6-weeks of daily oral escitalopram (escitalopram group N = 29); all patients received the same psychological support. Behavioural measures of affective bias as well as subjective measures of depression were collected at baseline and at the primary 6-week endpoint, using an established computerised task (Facial Emotion Recognition Task) and Quick Inventory of Depressive Symptomatology, respectively. Change in affective bias was further correlated with change in depression scores measured concurrently as well as at 1-month post-trial follow-up (week-10), corrected for baseline depression severity. Negative bias in facial expression recognition decreased after both treatments to a comparable level. Concurrently, change in negative affective bias was not associated with change in depression. Longitudinally, a decrease in the misclassification of positive faces as negative was associated with a decrease in depression scores at week-10 for the escitalopram group only. Therefore, a more positive behavioural bias in emotional processing was seen following psilocybin and citalopram compared to baseline. This highlights the potential for at least some overlap in cognitive mechanisms across two distinct treatments, which is noteworthy given the short dosing regimen with psilocybin.", "journal": null, "publication_date": "2025-11-12", "publication_year": 2025, "doi": "10.1038/s41398-025-03693-w", "pubmed_id": "41257994", "source_url": "https://doi.org/10.1038/s41398-025-03693-w", "keywords": "Humans, Citalopram, Hallucinogens, Treatment Outcome, Double-Blind Method, Depression, Affect, Adult, Middle Aged, Female, Male, Facial Recognition, Psilocybin, Escitalopram, Secondary Data Analysis", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"41257994\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Emotional Processing,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 408, "title": "Efficacy, all-cause discontinuation, and safety of serotonergic psychedelics and MDMA to treat mental disorders: A living systematic review with meta-analysis.", "normalized_title": "efficacy all cause discontinuation and safety of serotonergic psychedelics and mdma to treat mental disorders a living systematic review with meta analysis", "authors": "Højlund M, Kafali HY, Kırmızı B, Fusar-Poli P, Correll CU, Cortese S, Sabé M, Fiedorowicz J, Saraf G, Zein J, Berk M, Husain MI, Rosenblat JD, Rubaiyat R, Corace K, Wong S, Hatcher S, Kaluzienski M, Yatham LN, Cipriani A, Gosling CJ, Carhart-Harris R, Tanuseputro P, Myran DT, Fabiano N, Moher D, Mayo LM, Nicholls SG, White T, Prisco M, Radua J, Vieta E, Ladha KS, Katz J, Veroniki AA, Solmi M.", "abstract": "Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in disease-specific symptoms and all-cause discontinuation. Standardized mean differences (SMD) and relative risk (RR) were estimated using random-effects meta-analysis. Risk of bias (RoB) was assessed with Cochrane's RoB-tool version 2 and certainty of evidence with GRADE. The review is maintained as living systematic review (https://ebipsyche-database.org/). We included 30 RCTs (1480 participants; female=45.8 %; with psychological support=83.3 %; high RoB=83.3 %). In post-traumatic stress disorder (PTSD), MDMA reduced PTSD symptoms compared to any control (k = 11; SMD=-0.85 [-1.09; -0.60]; I2=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms (k = 8; SMD=-0.62 [-0.97; -0.28]; I2=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMDMDMA=-1.18 [-2.04; -0.32]; I2=0 %; k = 2; GRADE=low and SMDserotonergic=-0.88 [-1.70; -0.06]; I2=54 %;k = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates (k = 6; RR=1.42 [0.89; 2.26]; I2=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms (k = 1; SMD=0.22 [-0.32; 0.76]; GRADE=very low). Moderate certainty in evidence was only found for MDMA on PTSD symptoms when compared to placebo. MDMA/serotonergic psychedelics were not associated with higher risk of all-cause discontinuation (RRMDMA=0.74 [0.32; 1.72]; RRserotonergic=0.81 [0.56; 1.15]). Overall, MDMA/serotonergic psychedelics are promising for the treatment of PTSD, MDD, and anxiety disorders with moderate to large effect sizes. Pragmatic trials, long-term, head-to-head trials exploring the role of psychological support, aiming to identify predictors of response, and accounting for expectancy and functional unblinding are needed. Studies addressing these limitations will likely be required for regulatory approval of psychedelic drugs.", "journal": null, "publication_date": "2025-11-06", "publication_year": 2025, "doi": "10.1016/j.euroneuro.2025.09.011", "pubmed_id": "41205366", "source_url": "https://doi.org/10.1016/j.euroneuro.2025.09.011", "keywords": "Humans, N-Methyl-3,4-methylenedioxyamphetamine, Serotonin Agents, Hallucinogens, Treatment Outcome, Mental Disorders, Randomized Controlled Trials as Topic", "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\":\"41205366\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,PTSD,Addiction,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 325, "title": "Corrigendum to \"The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression\" [Journal of Affective Disorders, Volume 372 (2025), Pages 523-532].", "normalized_title": "corrigendum to the role of the psychedelic experience in psilocybin treatment for treatment resistant depression journal of affective disorders volume 372 2025 pages 523 532", "authors": "Goodwin GM, Aaronson ST, Alvarez O, Carhart-Harris R, Chai-Rees J, Croal M, DeBattista C, Dunlop BW, Feifel D, Hellerstein DJ, Husain MI, Kelly JR, Kirlic N, Licht RW, Marwood L, Meyer TD, Mistry S, Nowakowska A, Páleníček T, Repantis D, Schoevers RA, Simmons H, Somers M, Teoh E, Tsai J, Wahba M, Williams S, Young AH, Young MB, Zisook S, Malievskaia E.", "abstract": "", "journal": null, "publication_date": "2025-10-09", "publication_year": 2025, "doi": "10.1016/j.jad.2025.120352", "pubmed_id": "41075579", "source_url": "https://doi.org/10.1016/j.jad.2025.120352", "keywords": "", "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\":\"41075579\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 457, "title": "N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences.", "normalized_title": "n n dimethyltryptamine effects on connectome harmonics subjective experience and comparative psychedelic experiences", "authors": "Vohryzek J, Luppi AI, Atasoy S, Deco G, Carhart-Harris RL, Timmermann C, 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 N,N-dimethyltryptamine (DMT) is reshaped in line with other reported psychedelic compounds - psilocybin, lysergic acid diethylamide (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 index the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.", "journal": null, "publication_date": "2025-09-11", "publication_year": 2025, "doi": "10.1038/s41386-025-02190-4", "pubmed_id": "40940591", "source_url": "https://doi.org/10.1038/s41386-025-02190-4", "keywords": "Brain, Nerve Net, Humans, N,N-Dimethyltryptamine, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Adult, Female, Male, Young Adult, Connectome, Psilocybin", "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\":\"40940591\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Mechanism of Action,Consciousness,Aging", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3775, "title": "Blunted psychedelic drug effects in older adults", "normalized_title": "blunted psychedelic drug effects in older adults", "authors": "Aday JS, Carhart-Harris R, Boehnke KF.", "abstract": "Classic psychedelic drugs, including psilocybin, lysergic acid diethylamide, and ayahuasca/N,N-dimethyltryptamine, are increasingly being studied as therapeutics for myriad health conditions; however, predicting individual responses is notoriously difficult. An arguably underappreciated variable potentially moderating responses to psychedelics is age. Older adults exhibit unique pathogenesis of various neuropsychiatric disorders and, accordingly, have unique treatment considerations. In the case of psychedelics, differences in life circumstances, peripheral physiology, polypharmacy, weight, and neurobiology may present unique theoretical risks and opportunities for older adults. Here, we overview increased interest in studying psychedelics in older adults and spotlight an overlooked but consistent trend that has emerged in the literature-blunted psychedelic drug effects across the lifespan.", "journal": "PsyArXiv", "publication_date": "2025-09-03", "publication_year": 2025, "doi": "10.31234/osf.io/yz4cd_v2", "pubmed_id": null, "source_url": "https://doi.org/10.31234/osf.io/yz4cd_v2", "keywords": "", "substance_tags": "psilocybin", "source_name": "PsyArXiv", "date_added": "2026-07-01 11:10:20", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR1079275\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"PsyArXiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Aging,Longevity,Older Adults,Safety", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3240, "title": "Blunted psychedelic drug effects in older adults", "normalized_title": "blunted psychedelic drug effects in older adults", "authors": "Aday JS, Carhart-Harris R, Boehnke KF.", "abstract": "Classic psychedelic drugs, including psilocybin, lysergic acid diethylamide, and ayahuasca/N,N-dimethyltryptamine, are increasingly being studied as therapeutics for myriad health conditions; however, predicting individual responses is notoriously difficult. An arguably underappreciated variable potentially moderating responses to psychedelics is age. Older adults exhibit unique pathogenesis of various neuropsychiatric disorders and, accordingly, have unique treatment considerations. In the case of psychedelics, differences in life circumstances, peripheral physiology, polypharmacy, weight, and neurobiology may present unique theoretical risks and opportunities for older adults. Here, we overview increased interest in studying psychedelics in older adults and spotlight an overlooked but consistent trend that has emerged in the literature-blunted psychedelic drug effects across the lifespan.", "journal": "PsyArXiv", "publication_date": "2025-09-02", "publication_year": 2025, "doi": "10.31234/osf.io/yz4cd_v1", "pubmed_id": null, "source_url": "https://doi.org/10.31234/osf.io/yz4cd_v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "PsyArXiv", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR1078724\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"PsyArXiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Aging,Longevity,Older Adults,Safety", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 415, "title": "Short- and long-term modulation of rat prefrontal cortical activity following single doses of psilocybin.", "normalized_title": "short and long term modulation of rat prefrontal cortical activity following single doses of psilocybin", "authors": "Purple RJ, Gupta R, Thomas CW, Golden CT, Palomero-Gallagher N, Carhart-Harris R, Froudist-Walsh S, Jones MW.", "abstract": "We quantify cellular- and circuit-resolution neural network dynamics following therapeutically relevant doses of the psychedelic psilocybin. Using chronically implanted Neuropixels probes, we recorded local field potentials (LFP) alongside action potentials from hundreds of neurons spanning infralimbic, prelimbic and cingulate subregions of the medial prefrontal cortex of freely-behaving adult rats. Psilocybin (0.3 mg/kg or 1 mg/kg i.p.) unmasked 100 Hz high frequency oscillations that were most pronounced within the infralimbic cortex, persisted for approximately 1 h post-injection and were accompanied by decreased net neuronal firing rates and reduced spike-train complexity. These acute effects were more prominent during resting behaviour than during performance of a sustained attention task. LFP1-, 2- and 6-days post-psilocybin showed gradually-emerging increases in beta and low-gamma (20-60 Hz) power, specific to the infralimbic cortex. These findings reveal features of psychedelic action not readily detectable in human brain imaging, implicating infralimbic network oscillations as potential biomarkers of psychedelic-induced network plasticity over multi-day timescales.", "journal": null, "publication_date": "2025-08-25", "publication_year": 2025, "doi": "10.1038/s41380-025-03182-y", "pubmed_id": "40858779", "source_url": "https://doi.org/10.1038/s41380-025-03182-y", "keywords": "Prefrontal Cortex, Neurons, Animals, Rats, Rats, Sprague-Dawley, Hallucinogens, Action Potentials, Time Factors, Male, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"40858779\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,Brain Imaging,Biomarkers,Aging,Animal Study", "study_type": "Animal Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 560, "title": "Psychedelic Therapy, Positive Emotional Experiences, and the Central Role of Self-Compassion", "normalized_title": "psychedelic therapy positive emotional experiences and the central role of self compassion", "authors": "Zeifman R, Danias G, Agin-Liebes G, Pagni B, Kettner H, Bhat V, Ross S, Erritzoe D, Carhart-Harris R.", "abstract": "Abstract Background: Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional experiences and their association with improvements in mental health. Methods: Study 1 was an observational study of naturalistic psychedelic use. Study 2 used data from a clinical trial that compared psilocybin with escitalopram in individuals with major depressive disorder. In this trial, participants completed two dosing sessions, where they received either 25mg or 1mg of psilocybin. In both studies, following their psychedelic experience or psilocybin dosing sessions, participants rated their acute experiences of seven specific positive emotional experiences (self-compassion, compassion toward others, gratitude, love, awe, ecstasy, and peace). Results: Relative to low-dose psychedelic, medium and high-dose psychedelic use were associated with greater positive emotional experiences. Relative to 1mg psilocybin, 25mg psilocybin was associated with greater positive emotional experiences. Several positive emotional experiences predicted improvements in mental health and mediated treatment outcomes, with the strongest evidence for the effect of self-compassion (over and above mystical experience and positive mood). Discussion: Positive emotional experiences, especially self-compassion, appear to play an important role within psychedelic therapy. Based on these findings, we highlight key considerations surrounding psychotherapeutic approaches to, and optimization of, psychedelic therapy. Future research should move beyond retrospective, self-reports of emotional experiences to fully capture their role within psychedelic therapy.", "journal": "Research Square", "publication_date": "2025-08-21", "publication_year": 2025, "doi": "10.21203/rs.3.rs-7420529/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-7420529/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR1071953\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Emotional Processing,Mystical Experience,Clinical Trial,Observational Study", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 571, "title": "Improved mental health outcomes and normalised spontaneous EEG activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat.", "normalized_title": "improved mental health outcomes and normalised spontaneous eeg activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat", "authors": "Blest-Hopley G, Pasculli G, Ruffell SGD, Tsang W, Emmanuel O, Pate KM, Kettner H, Roseman L, Erritzoe D, Carhart-Harris R.", "abstract": "IntroductionPsilocybin, a serotonergic psychedelic, has shown therapeutic potential in treating mental health disorders by, amongst the many effects, promoting neuroplasticity and reorganising functional connectivity across cortical and subcortical networks involved in emotion and cognition. Veterans with traumatic brain injuries (TBI) often experience chronic neurological and psychological symptoms such as post-traumatic stress disorder (PTSD) and depression. This study investigates the effects of psilocybin administered in retreat settings on veterans with a history of TBI, focusing on mental health outcomes and changes in brain connectivity as measured by EEG.MethodsA total of 21 participants were recruited through the Heroic Hearts Project, which facilitated access to two six-day psilocybin retreats in Jamaica. Before the retreat, participants underwent three individual and three group coaching sessions to prepare for the experience. During the retreat, two psilocybin ceremonies were held, spaced 48 hours apart. Participants received an initial dose of 1.5g to 3.5g of dried psilocybin mushrooms, with the option to increase the second dose up to 5g. Psilocybin was administered in a tea format, under the supervision of experienced facilitators. Psychological outcomes were assessed using validated questionnaires (PCL-5, PHQ-9, STAI) at baseline (four weeks pre-retreat) and four weeks post-retreat. Electroencephalography (EEG) was used to measure brainwave activity pre- and post-treatment. Paired t-tests were used to analyze changes in psychological scores, while EEG frequency band analysis assessed changes in brain function and connectivity.ResultsImprovements were observed across several mental health measures: PTSD (PCL-5 scores decreased by 50%, p=0.010), depression (PHQ-9 scores decreased by 65%, p", "journal": null, "publication_date": "2025-08-05", "publication_year": 2025, "doi": "10.3389/fpsyt.2025.1594307", "pubmed_id": "40842948", "source_url": "https://doi.org/10.3389/fpsyt.2025.1594307", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"40842948\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,PTSD,Neuroplasticity,Brain Imaging,Emotional Processing,Veterans", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 578, "title": "Perturbing whole-brain models of brain hierarchy: An application for depression following pharmacological treatment.", "normalized_title": "perturbing whole brain models of brain hierarchy an application for depression following pharmacological treatment", "authors": "Socoró-Garrigosa M, Perl YS, Kringelbach ML, Erritzoe D, Nutt DJ, Carhart-Harris R, Vohryzek J, Deco G.", "abstract": "Determining the scale of neural representations is a central challenge in neuroscience. While localized representations have traditionally dominated, evidence suggests information is also encoded in distributed, hierarchical networks. Recent research indicates that the hierarchy of causal influences shaping functional patterns serves as a signature of distinct brain states, with implications for neuropsychiatric disorders. Here, we first explore how whole-brain models, guided by the thermodynamics of mind framework, estimate brain hierarchy and how perturbing such models enables the study of in-silico transitions represented by static functional connectivity. We then apply this to major depressive disorder, where different brain hierarchical reconfigurations emerge following psilocybin and escitalopram treatments. We build resting-state whole-brain models of depressed patients before and after interventions and conduct a dynamic sensitivity analysis to explore brain states' susceptibility-measuring their capacity to change-and their drivability to healthier states. We show that susceptibility is on average reduced by escitalopram and increased by psilocybin, and that both treatments promote healthier transitions. These results align with the post-treatment window of plasticity opened by serotonergic psychedelics and the similar clinical efficacy of both drugs in trials. Overall, this work demonstrates how whole-brain models of brain hierarchy can inform in-silico neurostimulation protocols for neuropsychiatric disorders.", "journal": null, "publication_date": "2025-07-20", "publication_year": 2025, "doi": "10.1111/nyas.15391", "pubmed_id": "40689865", "source_url": "https://doi.org/10.1111/nyas.15391", "keywords": "Brain, Humans, Citalopram, Hallucinogens, Depression, Models, Neurological, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"40689865\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Neuroplasticity", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "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" }, { "id": 625, "title": "Correction: Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises.", "normalized_title": "correction dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises", "authors": "Harding R, Singer N, Wall MB, Hendler T, Erritzoe D, Nutt D, Carhart-Harris R, Roseman L.", "abstract": "", "journal": null, "publication_date": "2025-06-30", "publication_year": 2025, "doi": "10.1038/s41380-025-03066-1", "pubmed_id": "40481249", "source_url": "https://doi.org/10.1038/s41380-025-03066-1", "keywords": "", "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\":\"40481249\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 623, "title": "Exploring the Therapeutic Effects of Psychedelics Administered to Military Veterans in Naturalistic Retreat Settings.", "normalized_title": "exploring the therapeutic effects of psychedelics administered to military veterans in naturalistic retreat settings", "authors": "Calnan M, Blest-Hopley G, Busch C, Adams M, Ruffell SGD, Piper T, Roseman L, Kettner H, Carhart-Harris R.", "abstract": "BackgroundMilitary veterans are at risk of various mental health conditions, with profound implications for post-deployment quality of life. Current treatment options encounter high dropout rates and non-responsiveness, and overlook the importance of community building in veterans' holistic recovery. Preliminary research suggests psychedelics offer therapeutic benefits for depression and post-traumatic stress disorder (PTSD) in veterans. Integrating psychedelic therapies with a communal retreat setting could provide a more holistic framework for improving veterans' well-being.ObjectivesTo evaluate the effects of psychedelic retreats on mental health and community reintegration in veterans.MethodsFifty-eight veterans attended psilocybin or ayahuasca retreats. Participants completed eight mental health questionnaires (e.g. PTSD Checklist, PCL-5; Patient Health Questionnaire, PHQ-9), and the Military to Civilian Questionnaire (M2C-Q) up to 4 weeks both pre- and post-retreat. Paired t-tests analyzed changes in outcome responses between time points, and gender and substance-specific analysis was conducted. Baseline scores were correlated with improvements in PCL-5 and PHQ-9 to investigate the relationship between initial symptom severity and percentage improvement following the retreat.ResultsSignificant improvements were found for all eight outcomes post-retreat, with the greatest percentage improvements found for depression (PHQ-9; 29.1%) and PTSD (PCL-5; 26.1%). Veterans attending psilocybin retreats showed greater improvements in seven out of eight outcomes, whereas ayahuasca retreats demonstrated greater improvements in PCL-5 scores for PTSD (ayahuasca: 26.4%; Psilocybin 24.8%). Male participants experienced greater improvements across all outcomes apart from the PCL-5 for PTSD (Male: 24.1%; Female: 32.1%). Higher baseline scores on the PCL-5 (PTSD) and PHQ-9 (depression), indicating worse initial mental health, correlated with greater outcome improvements.ConclusionsThis is the first study to investigate psychedelic retreats as a holistic therapy for veterans' mental health alongside community reintegration. Psilocybin and ayahuasca retreats significantly improved veterans' mental well-being, quality of life, PTSD, anxiety, depression, sleep, concussion, and post-deployment reintegration. Participants with more severe symptoms have the potential to benefit most from this intervention, with nuanced insight into improved outcomes based on gender and type of substance. Psychedelic retreats could provide a treatment framework to aid veterans' recovery by addressing psychological well-being, communal factors, and reintegration into civilian life.", "journal": null, "publication_date": "2025-06-30", "publication_year": 2025, "doi": "10.1002/brb3.70660", "pubmed_id": "40619953", "source_url": "https://doi.org/10.1002/brb3.70660", "keywords": "Humans, Banisteriopsis, Hallucinogens, Treatment Outcome, Depression, Stress Disorders, Post-Traumatic, Quality of Life, Adult, Middle Aged, Veterans, Female, Male, Surveys and Questionnaires, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"40619953\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,PTSD,Wellbeing,Observational Study,Veterans,Safety", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 497, "title": "Single-dose (10 mg) psilocybin reduces symptoms in adults with obsessive-compulsive disorder: A pharmacological challenge study.", "normalized_title": "single dose 10 mg psilocybin reduces symptoms in adults with obsessive compulsive disorder a pharmacological challenge study", "authors": "Pellegrini L, Fineberg NA, O'Connor S, De Souza AMFLP, Godfrey K, Reed S, Peill J, Healy M, Rohani-Shukla C, Lee H, Carhart-Harris R, Robbins TW, Nutt D, Erritzoe D.", "abstract": "BackgroundObsessive-compulsive disorder (OCD) is a common and disabling condition. A large proportion of patients fail to respond to first-line treatment with serotonin reuptake inhibitors either selective serotonin reuptake inhibitors (SSRIs) or clomipramine. Preliminary evidence suggests psilocybin, a serotonin receptor agonist, might be efficacious. We conducted a pharmacological challenge study to investigate the efficacy and mechanisms of effect of psilocybin in OCD. This analysis reports the clinical outcomes only.MethodsParticipants with a diagnosis of OCD of at least moderate severity, received two single doses of oral psilocybin, 1 mg followed by 10 mg, administered in fixed order separated by 4 weeks. On the day of dosing, they were treated in a day-care facility in the presence of clinicians experienced in the use of psychedelics for treating mental disorders. Psychological support was provided before, during and after dosing. Participants and raters were blinded to the order of treatment. They were assessed on the day before each dose (baseline 1, 2), on the day of dosing and at intervals over a 4-week period afterward using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (primary clinical outcome) and secondary clinical outcomes including the Montgomery-Åsberg Depression Rating Scale (MADRS). Adverse effects were also recorded.ResultsNineteen adult participants (aged 20-60) entered the study and 18 completed all assessments. Clinical outcomes following 1 mg and 10 mg psilocybin were compared using a linear mixed-effects model and ANOVA. A significant between-dosage effect favouring 10 mg psilocybin was found one-week after dosing on the Y-BOCS (Cohen's d = 0.82, p = 0.002). In particular, the effect one-week after dosing was statistically significant on the compulsion subscale of the Y-BOCS (Cohen's d: 0.74, p = 0.003), compared to obsession (Cohen's d: 0.50, p = 0.06). The effect diminished over the subsequent 3 weeks. No effect of psilocybin was detected on the MADRS. Psilocybin was well tolerated, with few adverse events reported at both dosages and no serious adverse events.ConclusionsIn this study, which was limited by a small sample size and the absence of randomisation, a 10 mg dose of oral psilocybin was found to be well-tolerated and potentially efficacious in patients with OCD. Psilocybin produced a rapid-onset, moderate to large effect on compulsive symptoms, which lasted up to one week after dosing. Future randomised placebo-controlled clinical trials investigating a longer course of multiple weekly doses of 10 mg psilocybin are indicated in OCD and in other obsessive-compulsive and related disorders characterised by compulsions.", "journal": null, "publication_date": "2025-06-30", "publication_year": 2025, "doi": "10.1016/j.comppsych.2025.152619", "pubmed_id": "40618640", "source_url": "https://doi.org/10.1016/j.comppsych.2025.152619", "keywords": "Humans, Hallucinogens, Treatment Outcome, Obsessive-Compulsive Disorder, Psychiatric Status Rating Scales, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"40618640\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,OCD,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Healthcare Workers,Adverse Events", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 584, "title": "The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial.", "normalized_title": "the effects of psilocybin therapy versus escitalopram on cognitive bias a secondary analysis of a randomized controlled trial", "authors": "Henry J, Giribaldi B, Nutt DJ, Erritzoe D, Carhart-Harris R, Lyons T.", "abstract": "BackgroundPatients with Major Depressive Disorder (MDD) have more dysfunctional attitudes than healthy individuals and these pessimistic biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in depression.MethodsSecondary analysis of a two-arm randomized controlled trial assessing the effect of psilocybin therapy versus escitalopram on 'maladaptive' cognitive biases relevant to the construct of depression. Primary outcomes were post-treatment changes in biases at six weeks compared with baseline, as measured using three validated psychological scales.FindingsFifty-nine MDD patients were randomly allocated to the psilocybin (n = 30) or escitalopram (n = 29) groups. Self-reported optimism showed a large increase six-weeks after psilocybin treatment (Mdiff=6·63 p < 0·0001; 95 % CI [4·06, 9·20], d = 1·1), whereas there was no change following escitalopram (Mdiff=1·52, p = 0·205; 95 % CI [-0·59, 3·62], d = 0·4). Behavioral results found that patients were more optimistic about desirable life events after psilocybin treatment (Mdiff=0·16, p = 0·0002; 95 % CI [0·08, 0·23], d = 1·1), but they were also less pessimistic about negative life events after escitalopram treatment (Mdiff=0·07, p = 0·018; 95 % CI [0·01, 0·13], d = 0·5). We found improvements in all three domains of dysfunctional attitudes following psilocybin treatment: achievement (Mdiff=10·37, p < 0·0001; 95 % CI [6·38, 14·53], d = 1·0); dependency (Mdiff=7·97, p < 0·0001; 95 % CI [4·00, 11·93], d = 0·9) and self-control (Mdiff=6·40, p = 0·0006; 95 % CI [2·60, 10·20], d = 0·8)), whereas only the achievement domain improved after escitalopram (Mdiff=4·10, p = 0·005; 95 % CI [1·35, 6·86], d = 0·6).InterpretationThese results suggest that two high-dose sessions with psilocybin therapy are superior to a six-week daily course of a selective serotonin-reuptake inhibitor antidepressant, in remediating negative cognitive biases in depression.", "journal": null, "publication_date": "2025-06-22", "publication_year": 2025, "doi": "10.1016/j.euroneuro.2025.06.003", "pubmed_id": "40554997", "source_url": "https://doi.org/10.1016/j.euroneuro.2025.06.003", "keywords": "Humans, Citalopram, Hallucinogens, Treatment Outcome, Cognition, Psychiatric Status Rating Scales, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"40554997\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Receptor Pharmacology,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": "published" }, { "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" }, { "id": 664, "title": "Enhanced meaning in life following psychedelic use: converging evidence from controlled and naturalistic studies.", "normalized_title": "enhanced meaning in life following psychedelic use converging evidence from controlled and naturalistic studies", "authors": "Roseby W, Kettner H, Roseman L, Spriggs MJ, Lyons T, Peill J, Giribaldi B, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "IntroductionPsychedelics, such as psilocybin, are increasingly recognized for their propensity to elicit powerful subjective experiences that carry personal meaning. While research has demonstrated the capacity for these compounds to promote psychological wellbeing, it has yet to be shown to what extent they modulate \"meaning in life\", a specific contributor to mental and physical health.MethodsUsing the Meaning in Life Questionnaire (MLQ), we examined changes in meaning in life occurring across three different contexts of psychedelic use, including a randomized clinical trial of psilocybin for depression, controlled administration of psilocybin in a single-arm healthy volunteer study, and a naturalistic observational study following participants in psychedelic retreats. Meaning in life changes were analyzed with linear mixed models, and relationships to other predictors and outcomes were examined via Pearson correlations.ResultsAcross all contexts, the sub-factor \"presence of meaning\" was strongly increased after a psychedelic experience, while the sub-factor \"search for meaning\" was only weakly reduced. Enhancements of meaning in life were also moderately correlated with changes in measures of mental health, including mental wellbeing and depression severity. In line with previous research, we found that mystical, ego dissolution and emotional breakthrough experiences were correlated with an increase of meaning in life, with context-dependent differences in the strength of the association.DiscussionThe convergence of evidence from multiple studies shows that psychedelic use has a robust and long-lasting positive effect on meaning in life. We explore potential mechanisms of psychedelic-induced meaning enhancement and highlight the possible influences of psychosocial context on outcomes.", "journal": null, "publication_date": "2025-06-05", "publication_year": 2025, "doi": "10.3389/fpsyg.2025.1580663", "pubmed_id": "40547590", "source_url": "https://doi.org/10.3389/fpsyg.2025.1580663", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"40547590\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Wellbeing,Emotional Processing,Mystical Experience,Clinical Trial,Observational Study,Healthy Volunteers", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 675, "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": "ObjectivePsilocybin is an emerging intervention for depression that may be at least as effective as selective serotonin reuptake inhibitors (SSRIs), but effects of the two treatments on the neural correlates of emotional processing have never been directly compared.MethodsThe authors assessed neural responses to emotional faces using blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) in two groups with major depression. One group (N=25; 9 women and 16 men) received two dosing sessions with 25 mg psilocybin plus 6 weeks of daily inert placebo, and the second group (N=21; 6 women and 15 men) received 6 weeks of escitalopram plus two dosing sessions with a nonpsychoactive (placebo) dose of 1 mg psilocybin. Both groups had equal psychological support throughout: 3 hours of preparation, one in-person integration session following the psilocybin dosing sessions, and two further integration sessions conducted via video call or telephone. An emotional face fMRI paradigm was completed before treatment and at the 6-week posttreatment primary end point (3 weeks following psilocybin dosing sessions).ResultsPatient group (psilocybin versus escitalopram) interacted with time point (before versus after treatment) on a distributed set of cortical regions. Post hoc within-condition analyses showed that posttreatment BOLD responses to emotional faces of all types were significantly reduced in the escitalopram group, with no change or a slight increase in the psilocybin group. Analyses of amygdala responsivity showed a reduction of response to fearful faces in the escitalopram group, but lesser effects for the psilocybin group.ConclusionsDespite large improvements in depressive symptoms in the psilocybin group, psilocybin therapy had only a minor effect on brain responsiveness to emotional stimuli. These results are consistent with prior findings that the antidepressant action of SSRIs is often accompanied by a reduction in emotional responsiveness, but this effect may not occur in psychedelic therapy.", "journal": null, "publication_date": "2025-05-06", "publication_year": 2025, "doi": "10.1176/appi.ajp.20230751", "pubmed_id": "40329640", "source_url": "https://doi.org/10.1176/appi.ajp.20230751", "keywords": "Brain, Amygdala, Humans, Hallucinogens, Magnetic Resonance Imaging, Facial Expression, Treatment Outcome, Double-Blind Method, Emotions, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"40329640\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Receptor Pharmacology,Aging,Emotional Processing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 631, "title": "Dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises.", "normalized_title": "dissociable effects of psilocybin and escitalopram for depression on processing of musical surprises", "authors": "Harding R, Singer N, Wall MB, Hendler T, Erritzoe D, Nutt D, Carhart-Harris R, Roseman L.", "abstract": "Psilocybin therapy (PT) is emerging as an effective intervention for Major Depressive Disorder (MDD), offering comparable efficacy to conventional treatments like selective serotonin reuptake inhibitors (SSRIs). Music, an emotionally evocative stimulus, provides a valuable tool to explore changes in hedonic and predictive processing mechanisms via expectancy violations, or 'surprises'. This study sought to compare behavioural and functional magnetic resonance imaging (fMRI) responses to musical surprises in MDD patients treated with either PT or the SSRI, escitalopram. In this secondary analysis of a trial, 41 MDD patients (with usable fMRI data) were randomly assigned to either PT (n = 22) or escitalopram (n = 19) treatment groups. Participants listened to music during fMRI and tracked their emotional experience, both before and after a 6-week intervention. Surprise-related valence and arousal indices were calculated. Musical surprises were entered as regressors for whole-brain and region of interest fMRI analyses. PT caused a greater decrease in anhedonia scores compared with escitalopram. While escitalopram led to reductions in surprise-related affective responses, PT showed no significant change. Escitalopram was associated with increased activation in memory and emotional processing areas during musical surprises (versus control events) when compared with PT. Following PT, there was decreased activation in the ventromedial prefrontal cortex and angular gyrus, and greater activation in sensory regions. PT may allow for the subjective response to musical surprises to be maintained through a lasting reduction in the salience of prediction errors, or, alternatively, by increasing hedonic priors. Contrastingly, escitalopram may diminish hedonic priors, highlighting fundamental differences in treatment mechanisms.", "journal": null, "publication_date": "2025-04-25", "publication_year": 2025, "doi": "10.1038/s41380-025-03035-8", "pubmed_id": "40281226", "source_url": "https://doi.org/10.1038/s41380-025-03035-8", "keywords": "Brain, Humans, Citalopram, Magnetic Resonance Imaging, Emotions, Auditory Perception, Music, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"40281226\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Emotional Processing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 710, "title": "Neuroplasticity and psychedelics: A comprehensive examination of classic and non-classic compounds in pre and clinical models.", "normalized_title": "neuroplasticity and psychedelics a comprehensive examination of classic and non classic compounds in pre and clinical models", "authors": "Agnorelli C, Spriggs M, Godfrey K, Sawicka G, Bohl B, Douglass H, Fagiolini A, Parastoo H, Carhart-Harris R, Nutt D, Erritzoe D.", "abstract": "Neuroplasticity, the ability of the nervous system to adapt throughout an organism's lifespan, offers potential as both a biomarker and treatment target for neuropsychiatric conditions. Psychedelics, a burgeoning category of drugs, are increasingly prominent in psychiatric research, prompting inquiries into their mechanisms of action. Distinguishing themselves from traditional medications, psychedelics demonstrate rapid and enduring therapeutic effects after a single or few administrations, believed to stem from their neuroplasticity-enhancing properties. This review examines how classic psychedelics (e.g., LSD, psilocybin, N,N-DMT) and non-classic psychedelics (e.g., ketamine, MDMA) influence neuroplasticity. Drawing from preclinical and clinical studies, we explore the molecular, structural, and functional changes triggered by these agents. Animal studies suggest psychedelics induce heightened sensitivity of the nervous system to environmental stimuli (meta-plasticity), re-opening developmental windows for long-term structural changes (hyper-plasticity), with implications for mood and behavior. Translating these findings to humans faces challenges due to limitations in current imaging techniques. Nonetheless, promising new directions for human research are emerging, including the employment of novel positron-emission tomography (PET) radioligands, non-invasive brain stimulation methods, and multimodal approaches. By elucidating the interplay between psychedelics and neuroplasticity, this review informs the development of targeted interventions for neuropsychiatric disorders and advances understanding of psychedelics' therapeutic potential.", "journal": null, "publication_date": "2025-04-01", "publication_year": 2025, "doi": "10.1016/j.neubiorev.2025.106132", "pubmed_id": "40185376", "source_url": "https://doi.org/10.1016/j.neubiorev.2025.106132", "keywords": "Brain, Animals, Humans, Hallucinogens, Mental Disorders, Neuronal Plasticity", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"40185376\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Longevity,Review Article,Animal Study", "study_type": "Review Article", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3104, "title": "The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial", "normalized_title": "the effects of psilocybin therapy versus escitalopram on cognitive bias a secondary analysis of a randomized controlled trial", "authors": "Henry J, Giribaldi B, Nutt DJ, Erritzoe D, Carhart-Harris R, Lyons T.", "abstract": "Background Patients with Major Depressive Disorder (MDD) have more dysfunctional attitudes and pessimism than healthy individuals and these biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in MDD. Methods Secondary analysis of a two-arm, randomized controlled trial ( ClinicalTrials.gov Identifier: NCT03429075 ) assessing the effect of psilocybin therapy versus escitalopram on ‘maladaptive’ cognitive biases relevant to the construct of depression. Psilocybin group participants received two 25mg doses and escitalopram group received three weeks of daily 10mg, increased to 20mg for a following three weeks. Primary outcomes in this analysis were post-treatment changes in biases at six weeks compared with baseline, as measured using three validated psychological scales. Findings Fifty-nine MDD patients were randomly allocated to the psilocybin (n=30) or escitalopram (n=29) groups. Self-reported optimism showed a large and significant increase six-weeks after psilocybin treatment ( M diff =6·63 p", "journal": "medRxiv", "publication_date": "2025-03-20", "publication_year": 2025, "doi": "10.1101/2025.03.17.25324123", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2025.03.17.25324123", "keywords": "", "substance_tags": "psilocybin", "source_name": "medRxiv", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR993220\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"medRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,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" }, { "id": 3209, "title": "Psychedelics Align Brain Activity with Context", "normalized_title": "psychedelics align brain activity with context", "authors": "Stoliker D, Novelli L, Khajehnejad M, Biabani M, Greaves MD, Barta T, Williams M, Chopra S, Bazin O, Simonsson O, Chambers R, Barrett F, Deco G, Preller KH, Carhart-Harris R, Seth A, Sundram S, Egan GF, Razi A.", "abstract": "Psychedelics can profoundly alter consciousness by reorganising brain connectivity; however, their effects are context-sensitive. To understand how this reorganisation depends on context, we collected and comprehensively analysed the largest psychedelic neuroimaging dataset to date. Sixty-two adults were scanned with functional MRI and EEG during rest and naturalistic stimuli (meditation, music, and movie), before and after ingesting 19 mg of psilocybin (functional MRI ≈80 min post-dose; EEG ≈150 min post-dose). Half the participants ranked the experience among the most meaningful of their lives. Under psilocybin, functional MRI and EEG signals recorded during eyes-closed conditions became similar to those recorded during an eyes-open condition. Global functional connectivity increased in associative regions and decreased in sensory areas. Using machine learning to represent neural activity as low-dimensional trajectories, we found that psilocybin reorganised these into structured, context-sensitive patterns of brain activity that reflected both experimental condition and the quality of subjective experience, revealing an organisation that was missed by time-averaged connectivity measures. Under psilocybin, brain networks that ordinarily segregate internal and external processing coherently integrated and aligned neural dynamics with context. This context-alignment manifested as distinct and cohesive neural trajectories in participants reporting positively felt self- and boundary-dissolving effects, corresponding to the felt experience of being part of the environment, which we refer to as embeddedness -the subjective experience of being continuous with, rather than separate from, the surrounding environment. The strength of this context-alignment was associated with next-day mindset change, bridging the neural, experiential, and therapeutic dimensions of the psychedelic state. These findings show that the organisation of brain activity covaries with the experiential coherence of the psychedelic state, and provide a systems-level framework for how context-sensitive brain dynamics link neurobiology to subjective experience and behavioural change.", "journal": "bioRxiv", "publication_date": "2025-03-10", "publication_year": 2025, "doi": "10.1101/2025.03.09.642197", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2025.03.09.642197", "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\":\"PPR987866\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Consciousness,Aging", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3116, "title": "Revealing Changes in Linear and Nonlinear Functional Connectivity After Psilocybin and Escitalopram Treatment in Patients with Depression", "normalized_title": "revealing changes in linear and nonlinear functional connectivity after psilocybin and escitalopram treatment in patients with depression", "authors": "Quah S, Glick C, Roseman L, Pasquini L, Carhart-Harris R, Saggar M.", "abstract": "Major Depressive Disorder (MDD) is typically characterized by altered linear functional connectivity (FC) across large-scale brain networks. Yet, it is unclear whether similar alterations are observed when nonlinear FC is examined. This study investigated how antidepressant treatment (i.e., psilocybin and escitalopram) modulates both linear FC and nonlinear FC in individuals with MDD. Here, we focused specifically on five key canonical brain networks: the Default Mode Network (DMN), Frontoparietal Network (FPN), Salience Network (SAL), Dorsal Attention Network (DAN), and Ventral Attention Network (VAN). Across both treatments, using resting-state fMRI data, we first compared changes in linear and nonlinear FC between responders and non-responders. Responders exhibited increased linear FC within the VAN and greater nonlinear FC within the DMN and VAN than non-responders. We also observed more between-network linear FC for DMN-DAN and nonlinear FC for DMN-VAN in responders than non-responders. Next, we compared treatments and observed that Psilocybin responders showed greater connectivity between FPN-VAN (linear FC), DMN-VAN (nonlinear FC), and SAL-VAN (nonlinear FC) integration than Escitalopram responders, reflecting enhanced coordination and integration between higher-order networks. Conversely, Escitalopram responders exhibited reduced within-network linear FC within the DMN and SAL and between the DMN and VAN, consistent with a dampening of self-referential and salience processing and altered attentional control. These findings highlight potentially distinct mechanisms of action for psilocybin and escitalopram. Incorporating both linear and nonlinear FC analyses provided a novel characterization of these effects, emphasizing the role of these different interactions in antidepressant response. Future studies should investigate the long-term stability of these network changes and their relationship to clinical outcomes.", "journal": "bioRxiv", "publication_date": "2025-03-09", "publication_year": 2025, "doi": "10.1101/2025.03.05.641592", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2025.03.05.641592", "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\":\"PPR987622\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Mechanism of Action,Default Mode Network,Drug Interactions", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 712, "title": "Psilocybin for disorders of consciousness: A case-report study.", "normalized_title": "psilocybin for disorders of consciousness a case report study", "authors": "Cardone P, Núñez P, Alnagger NLN, Martial C, van der Lande GJM, Sandell R, Carhart-Harris R, Gosseries O.", "abstract": "ObjectiveWith very few treatments available, post-comatose disorders of consciousness (DoC) pose one of the hardest challenges in modern neurology. Following promising clinical trial results in psychiatry, and a deepening understanding of their brain mechanisms, psychedelics have been suggested as a novel therapeutic drug for DoC patients, given that they increase the entropy or complexity of spontaneous activity in healthy participants. However, no attempts have been so far performed in patients with DoC.MethodsIn this case report, we describe the first-ever administration of psilocybin, a classic psychedelic (i.e., agonist at the 5-HT2A receptor), to a patient in a minimally conscious state plus. We report the behavioural effects and changes in neurophysiology measured with EEG.ResultsWe report no increase in overt behavioural repertoire with validated scales, yet new spontaneous behaviour not previously seen, and increased brain complexity, as measured by the Lempel-Ziv complexity index, with changes in the underlying periodic rhythms.ConclusionsThis study contributes to future investigations exploring the use of psychedelics in DoC, enriching the discussion surrounding the role of psychedelics in medicine, and the link between brain complexity and consciousness.SignificanceThis is the first-ever report of a classic psychedelic used as a treatment for post-comatose DoC.", "journal": null, "publication_date": "2025-03-07", "publication_year": 2025, "doi": "10.1016/j.clinph.2025.02.264", "pubmed_id": "40147181", "source_url": "https://doi.org/10.1016/j.clinph.2025.02.264", "keywords": "Brain, Humans, Consciousness Disorders, Hallucinogens, Electroencephalography, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"40147181\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Mechanism of Action,Receptor Pharmacology,Consciousness,Clinical Trial,Case Report,Healthy Volunteers", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 793, "title": "A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research.", "normalized_title": "a field wide review and analysis of study materials used in psilocybin trials assessment of two decades of research", "authors": "Yaden DB, Graziosi M, Owen AM, Agin-Liebes G, Aaronson ST, Allen KE, Barrett FS, Bogenschutz MP, Carhart-Harris R, Ching THW, Cosimano MP, Danforth A, Davis AK, Garcia-Romeu A, Griffiths R, Grob CS, Gründer G, Gukasyan N, Heinzerling KG, Hendricks PS, Holze F, Horton DM, Johnson MW, Kelmendi B, Knatz Peck S, Koslowski M, Liechti ME, Mertens LJ, Moreno FA, Nayak SM, Nicholas CR, Preller KH, Rieser NM, Ross S, Sergi K, Sloshower J, Smigielski L, Stenbæk DS, Vollenweider FX, Weiss B, Wolff M, Yaden ME.", "abstract": "IntroductionSerotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.g., informed consent), and such documents and conversations can provide safety-related information-but may also introduce a wide range of expectancies. Such expectancies might involve the specific character of the acute subjective effects of psychedelics, possible side effects, and anticipated outcomes.MethodsTo better understand the content of this psychoeducation, we gathered study materials from many psilocybin studies conducted in the past two decades in healthy and therapeutic populations. We conducted a reflexive thematic analysis to better understand these documents.ResultsWhile these documents varied substantially between studies, we identified themes intended to lower levels of risk and optimize therapeutic effects from psychedelic treatments. The most frequently coded themes related to (1) biological and physical safety, (2) psychological safety and well-being, (3) aspects of setting, and (4) potential for expectancies. Prioritizing biological and psychological safety was evident in the materials from all sites. Furthermore, we identify potential contributors to expectancy unrelated to safety and suggest that these extrapharmacological elements be studied systematically in future research.ConclusionsIdeally, future research should strive to maximize safety while attempting to minimize extraneous expectancies.", "journal": null, "publication_date": "2025-02-26", "publication_year": 2025, "doi": "10.1089/psymed.2024.0019", "pubmed_id": "40351554", "source_url": "https://doi.org/10.1089/psymed.2024.0019", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"40351554\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Receptor Pharmacology,Consciousness,Wellbeing,Review Article,Safety,Adverse Events,Contraindications", "study_type": "Review Article", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 824, "title": "A qualitative analysis of the psychedelic mushroom come-up and come-down.", "normalized_title": "a qualitative analysis of the psychedelic mushroom come up and come down", "authors": "Brouwer A, Brown JK, Erowid E, Erowid F, Thyssen S, Raison CL, Carhart-Harris RL.", "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 an initially distressing but ultimately distress-resolving effect. Here we present a qualitative analysis of the self-reported 'come-up' or onset phase, and 'come-down' or falling phase, of the psychedelic experience. Focusing on psilocybin or psilocybin-containing mushroom experience reports submitted to Erowid.org, we use phenomenological, thematic content and word frequency analysis to show that the come-up is more often characterized by negatively valenced feeling states that resemble an acute stress reaction, while the come-down phase is more often characterized by positively valenced feeling states of the sort often observed following recovery from illness or resolution of stress. The therapeutic and theoretical relevance of these findings are discussed.", "journal": null, "publication_date": "2025-02-06", "publication_year": 2025, "doi": "10.1038/s44184-024-00095-6", "pubmed_id": "39915687", "source_url": "https://doi.org/10.1038/s44184-024-00095-6", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"39915687\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"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": "published" }, { "id": 845, "title": "Correction: Study Protocol for 'PsilOCD: A Pharmacological Challenge Study Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity'.", "normalized_title": "correction study protocol for psilocd a pharmacological challenge study evaluating the effects of the 5 ht2a agonist psilocybin on the neurocognitive and clinical correlates of compulsivity", "authors": "O'Connor S, Godfrey K, Reed S, Peill J, Rohani-Shukla C, Healy M, Robbins T, Frota Lisboa Pereira de Souza A, Tyacke R, Papasyrou M, Stenbæk D, Castro-Rodrigues P, Chiera M, Lee H, Martell J, Carhart-Harris R, Pellegrini L, Fineberg NA, Nutt D, Erritzoe D.", "abstract": "[This corrects the article DOI: 10.7759/cureus.78171.].", "journal": null, "publication_date": "2025-01-29", "publication_year": 2025, "doi": "10.7759/cureus.c209", "pubmed_id": "39897296", "source_url": "https://doi.org/10.7759/cureus.c209", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"39897296\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "OCD,Receptor Pharmacology", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 850, "title": "From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS).", "normalized_title": "from relaxed beliefs under psychedelics rebus to revised beliefs after psychedelics rebas", "authors": "Zeifman RJ, Spriggs MJ, Kettner H, Lyons T, Rosas FE, Mediano PAM, Erritzoe D, Carhart-Harris RL.", "abstract": "The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; which (b) facilitate positive therapeutic outcomes and are associated with the entropy of EEG signals. Healthy individuals (N = 11) were administered 1 mg and 25 mg psilocybin 4-weeks apart. Confidence ratings for personally held beliefs were obtained before, during, and 4-weeks post-psilocybin. Acute entropy and subjective experiences were measured, as was well-being (before and 4-weeks post-psilocybin). Confidence in negative self-beliefs decreased following 25 mg psilocybin. Entropy and subjective effects under 25 mg psilocybin correlated with decreases in negative self-belief confidence (acutely and at 4-weeks). Particularly strong evidence was seen for a relationship between decreases in negative self-belief confidence and increases in well-being. We report the first empirical evidence that the relaxation and revision of negative self-belief confidence mediates psilocybin's positive psychological outcomes, and provide tentative evidence for a neuronal mechanism, namely, increased neuronal entropy. Replication within larger and clinical samples is necessary. We also introduce a new measure for examining the robustness of these preliminary findings and the utility of the REBUS model.", "journal": null, "publication_date": "2025-01-28", "publication_year": 2025, "doi": "10.1038/s41598-023-28111-3", "pubmed_id": "39881126", "source_url": "https://doi.org/10.1038/s41598-023-28111-3", "keywords": "Humans, Hallucinogens, Electroencephalography, Adult, Female, Male, Young Adult, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"39881126\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Wellbeing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 848, "title": "Study Protocol for 'PsilOCD: A Pharmacological Challenge Study Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity'.", "normalized_title": "study protocol for psilocd a pharmacological challenge study evaluating the effects of the 5 ht2a agonist psilocybin on the neurocognitive and clinical correlates of compulsivity", "authors": "O'Connor S, Godfrey K, Reed S, Peill J, Rohani-Shukla C, Healy M, Robbins T, Frota Lisboa Pereira de Souza A, Tyacke R, Papasyrou M, Stenbæk D, Castro-Rodrigues P, Chiera M, Lee H, Martell J, Carhart-Harris R, Pellegrini L, Fineberg NA, Nutt D, Erritzoe D.", "abstract": "BackgroundObsessive-compulsive disorder (OCD) is a complex condition marked by persistent distressing thoughts and repetitive behaviours. Despite its prevalence, the mechanisms behind OCD remain elusive, and current treatments are limited. This protocol outlines an investigative study for individuals with OCD, exploring the potential of psilocybin to improve key components of cognition implicated in the disorder. The PsilOCD study strives to assess the effects of low-moderate psilocybin treatment (10 mg) alongside non-interventional therapy on several facets of OCD. The main focus points of PsilOCD are cognitive flexibility, measured with cognitive tests, and neuroplasticity, assessed through electroencephalography (EEG).Methods20 blinded participants with OCD will complete two dosing sessions, separated by four weeks, where they will receive 1 mg of psilocybin on the first and 10 mg on the second. The first dose serves as an active placebo, and the latter is a low-moderate dose that induces relatively mild-moderate emotional and perceptual effects. Participants will be supported by trained psychedelic therapists, who will sit with them during each dosing session and provide virtual preparation and integration sessions over the 12-week study period. Therapeutic support will be the same for both the 1 mg and 10 mg sessions. PsilOCD's primary outcomes include scores in the intradimensional-extradimensional (ID-ED) shift task, which is an established measure of cognitive flexibility, and neuroplasticity as quantified by a visual long-term potentiation (vLTP) task. This task is delivered as part of an EEG paradigm and measures acute quantified changes in neuroplasticity in the brain's visual system. The ID-ED task will be conducted twice, two days after each dosing session, and the EEG recordings will also be taken twice, immediately after each session. Secondary outcome assessments will include OCD and affective symptom severity, as well as an array of patient-reported outcome measures (PROMs), in the form of questionnaires designed to assess well-being, dissociable and well-established mood-related (affective) measures, and participants' subjective experience of the psilocybin experience.DiscussionThis study's results are expected to offer critical insights into the neural mechanisms underlying the effects of psilocybin-assisted therapy in treating OCD, and whether these correlate with changes in the cognitive features of the condition. As a secondary aim, it will ascertain whether a low, tolerable dose is a feasible and efficacious clinical treatment, and will provide crucial data to guide the design of a potential follow-up randomised control trial (RCT).", "journal": null, "publication_date": "2025-01-28", "publication_year": 2025, "doi": "10.7759/cureus.78171", "pubmed_id": "39882198", "source_url": "https://doi.org/10.7759/cureus.78171", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"39882198\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "OCD,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Wellbeing,Emotional Processing,Randomized Controlled Trial", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3201, "title": "Perturbing whole-brain models of brain hierarchy: an application for depression following pharmacological treatment", "normalized_title": "perturbing whole brain models of brain hierarchy an application for depression following pharmacological treatment", "authors": "Socoró Garrigosa M, Sanz Perl Y, Kringelbach ML, Carhart-Harris R, Vohryzek J, Deco G.", "abstract": "Neural representation can extend beyond localised activity to encompass global patterns, where information is distributed across brain networks in a hierarchical manner. Recent research suggests that the hierarchy of causal influences shaping these patterns can serve as a signature of distinct brain states, with implications for neuropsychiatric disorders. Here, we first delve into how whole-brain models, guided by the Thermodynamics of Mind framework, can estimate the brain hierarchy of specific brain states, and how perturbations of such models can study the in-silico transitions to other states represented by static functional connectivity. We then show an application for major depressive disorder, where different brain hierarchical reconfigurations have been found following psilocybin and escitalopram treatments. We build whole-brain models of depressed patients before and after psilocybin and escitalopram interventions, and we carry a dynamic sensitivity analysis to explore the susceptibility of brain states and their drivability to healthier states. We show that susceptibility is on average reduced by escitalopram and increased by psilocybin, and that both treatments succeed in promoting healthier transitions. These results align with the post-treatment window of plasticity opened by serotonergic psychedelics, as well as with the similar clinical efficacy of both drugs observed in clinical trials. Graphical Abstract We apply whole-brain models of brain hierarchy based on the Thermodynamics of Mind framework to investigate state transitions in depression. Dynamic sensitivity analysis explores how psilocybin and escitalopram affect susceptibility and drivability to healthier states. Results show that psilocybin increases susceptibility, while escitalopram reduces it, with both enabling optimal transitions. This pipeline demonstrates the promise of in-silico approaches to inform neurostimulation protocols, potentially enhancing or complementing antidepressant therapies.", "journal": "bioRxiv", "publication_date": "2025-01-01", "publication_year": 2025, "doi": "10.1101/2025.01.01.631011", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2025.01.01.631011", "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\":\"PPR962216\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Neuroplasticity,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3298, "title": "Brain dynamics of classical psychedelics show paradoxical hierarchical flattening with increased complexity", "normalized_title": "brain dynamics of classical psychedelics show paradoxical hierarchical flattening with increased complexity", "authors": "Vohryzek J, Garcia Guzman E, Kringelbach ML, Lopez-Sola E, Timmermann C, Roseman L, Tagliazucchi E, Ruffini G, Carhart-Harris R, Deco G, Sanz Perl Y.", "abstract": "Despite divergent behavioral and phenomenological profiles, both psychedelic states and reduced states of consciousness have been associated with a flattening of the brain's functional hierarchy. To address this apparent paradox, we developed a more specific definition of hierarchy based on the proximity of the brain to thermodynamic equilibrium and then applied it to investigate the changes to the functional hierarchy elicited by three classical serotonergic psychedelics: psilocybin, lysergic acid diethylamide, and dimethyltryptamine. We found that all three psychedelics consistently induced a global reduction in the functional hierarchy. In contrast to the flattening of the functional hierarchy observed during loss of consciousness, psychedelics displaced the brain towards equilibrium while simultaneously increasing the complexity of neural activity, indicating a unique mechanism linked to specific changes in the configuration and differentiation of resting-state networks. This work showcases how metrics based on statistical mechanics can be used for the specific characterization of different global brain states, contributing to the understanding of consciousness as a collective process emerging from complex neural interactions.", "journal": "bioRxiv", "publication_date": "2024-12-21", "publication_year": 2024, "doi": "10.1101/2024.12.21.629922", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2024.12.21.629922", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:50", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"PPR958078\",\"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" }, { "id": 808, "title": "The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.", "normalized_title": "the role of the psychedelic experience in psilocybin treatment for treatment resistant depression", "authors": "Goodwin GM, Aaronson ST, Alvarez O, Carhart-Harris R, Chai-Rees J, Croal M, DeBattista C, Dunlop BW, Feifel D, Hellerstein DJ, Husain MI, Kelly JR, Kirlic N, Licht RW, Marwood L, Meyer TD, Mistry S, Nowakowska A, Páleníček T, Repantis D, Schoevers RA, Simmons H, Somers M, Teoh E, Tsai J, Wahba M, Williams S, Young AH, Young MB, Zisook S, Malievskaia E.", "abstract": "ObjectiveTo determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.MethodsFor treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support. The resulting psychedelic experience (Five-Dimensional Altered States of Consciousness questionnaire [5D-ASC] and Emotional Breakthrough Inventory [EBI]) were measured. These proximal variables and outcome 3 weeks post-administration (change in Montgomery-Åsberg Depression Rating Scale [MADRS]) were explored using correlation analysis.ResultsThe mean intensity of psychedelic effects was dose-related, but distributions of scores for different doses overlapped considerably. Depression response correlated with select aspects of the psychedelic experience overall and for individual doses. At the 25 mg dose, 5D-ASC dimensions Oceanic Boundlessness (Pearson correlation coefficient r = -0.508) and Visual Restructuralization (r = -0.516), and EBI (r = -0·637) were the variables with the strongest correlation to the Week 3 change from Baseline in MADRS score.LimitationsThe existence of correlation does not establish causation and exploratory findings require further replication, preferably in larger independent samples.ConclusionsThe intensity of psychedelic experience overlaps widely across doses and mitigates the risk of unblinding to dose. Correlations between psychedelic experience and outcome suggest specificity in psilocybin's mechanism of action. Quality and intensity of psychedelic experience may be a measure of pharmacodynamic effect and reveal an effective dose response phenomenon for single oral doses.", "journal": null, "publication_date": "2024-12-17", "publication_year": 2024, "doi": "10.1016/j.jad.2024.12.061", "pubmed_id": "39706482", "source_url": "https://doi.org/10.1016/j.jad.2024.12.061", "keywords": "Humans, Hallucinogens, Treatment Outcome, Psychiatric Status Rating Scales, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant, Surveys and Questionnaires, Psilocybin, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"39706482\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Pharmacology,Mechanism of Action,Consciousness,Emotional Processing,Observational Study,Treatment-Resistant Depression,Safety", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 932, "title": "Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology.", "normalized_title": "synergistic multi level understanding of psychedelics three systematic reviews and meta analyses of their pharmacology neuroimaging and phenomenology", "authors": "Shinozuka K, Jerotic K, Mediano P, Zhao AT, Preller KH, Carhart-Harris R, Kringelbach ML.", "abstract": "Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: (1) subjective experience (phenomenology), (2) neuroimaging and (3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT2A, 5-HT2C, or D2 receptors, relative to the 5-HT1A receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.", "journal": null, "publication_date": "2024-12-03", "publication_year": 2024, "doi": "10.1038/s41398-024-03187-1", "pubmed_id": "39632810", "source_url": "https://doi.org/10.1038/s41398-024-03187-1", "keywords": "Brain, Humans, Dimethoxyphenylethylamine, Lysergic Acid Diethylamide, Hallucinogens, Neuroimaging, Psilocybin", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"39632810\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Addiction,Brain Imaging,Pharmacology,Receptor Pharmacology,Consciousness,Aging,Systematic Review,Review Article,Safety", "study_type": "Systematic Review", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 878, "title": "An investigation of acute physiological and psychological moderators of psychedelic-induced personality change among healthy volunteers.", "normalized_title": "an investigation of acute physiological and psychological moderators of psychedelic induced personality change among healthy volunteers", "authors": "Godfrey K, Weiss B, Zhang X, Spriggs M, Peill J, Lyons T, Carhart-Harris R, Erritzoe D.", "abstract": "This study investigated the effects of a single high-dose of psilocybin on personality traits in psychedelic-naïve healthy volunteers. These data originate from a larger within-subjects fixed-order design trial, where a single high dose of psilocybin (25 mg) was administered in a psychologically supportive setting and was compared against a (one-month) prior, 1 mg 'placebo' dose. Personality shifts were assessed by the Big Five Inventory and the Big Five Aspect Scale, while the Altered States of Consciousness questionnaire (5D-ASC) and the Psychological Insight Scale gauged the acute psychological effects of the substance. Electroencephalography provided neurophysiological insights, specifically examining alpha power and Lempel-Ziv complexity (LZc). Results indicated significant reductions in neuroticism one month after 25 mg psilocybin administration, a finding consistent with prior studies. Reductions in neuroticism were moderated by the subjective meaningfulness of the psychedelic experience, as well as by the dread of ego dissolution subscale of the 5D-ASC, suggesting a relationship between acute drug effects and enduring personality alterations. Thus, this study substantiates the role of acute psychedelic states in catalysing lasting personality transformations in a generally beneficial direction, with broader implications for therapeutic applications and understanding of personality dynamics.", "journal": null, "publication_date": "2024-12-01", "publication_year": 2024, "doi": "10.1016/j.nsa.2024.104092", "pubmed_id": "40654586", "source_url": "https://doi.org/10.1016/j.nsa.2024.104092", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"40654586\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Personality Change,Healthy Volunteers", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 970, "title": "Preliminary Evidence of Sleep Improvements Following Psilocybin Administration, and their Involvement in Antidepressant Therapeutic Action.", "normalized_title": "preliminary evidence of sleep improvements following psilocybin administration and their involvement in antidepressant therapeutic action", "authors": "Reid MJ, Kettner H, Blanken TF, Weiss B, Carhart-Harris R.", "abstract": "Purpose of the studyPsilocybin is a rapidly-emerging treatment for depression, yet its impact on sleep is not well understood. We sought to explore the literature on sleep and psilocybin use, and explore the topic using our own primary data.FindingsWhilst clinical trials demonstrate large depressive symptom improvements, the impact of psilocybin on sleep quality or insomnia symptoms, has not been directly studied. Using our own preliminary-data we demonstrated that both depressive-symptoms and sleep-disturbances decreased significantly following psilocybin use, though sleep improvements were smaller compared to depressive symptoms. More severe sleep-disturbances at baseline were linked to lower probability of depression remission, underscoring a potential interaction between sleep and psilocybin's efficacy. Addressing sleep disturbances could enhance therapeutic outcomes in psilocybin-assisted therapy and could lead to more effective, personalized treatment-strategies. Future research should focus on populations with sleep disorders, and on examining causal-pathways of sleep physiology's impact on psilocybin efficacy.", "journal": null, "publication_date": "2024-11-12", "publication_year": 2024, "doi": "10.1007/s11920-024-01539-8", "pubmed_id": "39532819", "source_url": "https://doi.org/10.1007/s11920-024-01539-8", "keywords": "Humans, Sleep Initiation and Maintenance Disorders, Hallucinogens, Antidepressive Agents, Depressive Disorder, Adult, Female, Male, Sleep Wake Disorders, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"39532819\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Clinical Trial,Drug Interactions", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "id": 840, "title": "Examining differences in the effects and contexts of naturalistic psilocybin use for White participants vs. Participants of Color: A longitudinal online survey study.", "normalized_title": "examining differences in the effects and contexts of naturalistic psilocybin use for white participants vs participants of color a longitudinal online survey study", "authors": "Jones G, Lowe MX, Nayak S, Sepeda N, Kettner H, Carhart-Harris R, Jackson H, Garcia-Romeu A.", "abstract": "BackgroundPsilocybin (a psychoactive compound found in \"magic mushrooms\" or \"shrooms\") has been gaining increased attention in research and popular culture as a number of clinical and observational studies have demonstrated that it may have potential for improving mental wellbeing. Relatedly, there has been a substantial uptick in naturalistic (e.g., real-world, non-clinical) psilocybin use in the United States. While a number of longitudinal studies have demonstrated that naturalistic psilocybin use is linked to positive mental health outcomes on average, few studies have examined how the effects of psilocybin and contexts for psilocybin use may differ for White populations compared to Populations of Color.ObjectiveTo examine differences in health outcomes, subjective effects, and contexts of naturalistic psilocybin use in White participants compared to Participants of Color.MethodsThis study used data from a large, online longitudinal study of individuals who planned to engage in naturalistic psilocybin use (N = 2833). We used mixed-effects models to assess whether race/ethnicity (White vs. Participant of Color) moderated associations between time (Time 2 [initial assessment point for longitudinal measures], Time 5 [2-4 weeks post-psilocybin experience, and Time 6 [2-3 months post-experience]) and outcomes related to mental health (depression, anxiety, spiritual wellbeing, cognitive flexibility, emotion regulation [expressive suppression + cognitive reappraisal]). We also used exploratory chi-squared tests to examine differences in contexts for psilocybin use as well as differences in subjective effects related to the psilocybin experience.ResultsRace/ethnicity moderated the associations between time for predicting spiritual wellbeing (beta = -1.8; 95 % CI [-3.4, -0.17]; p", "journal": null, "publication_date": "2024-10-21", "publication_year": 2024, "doi": "10.1016/j.jad.2024.10.058", "pubmed_id": "39447981", "source_url": "https://doi.org/10.1016/j.jad.2024.10.058", "keywords": "Humans, Hallucinogens, Longitudinal Studies, Mental Health, Adult, Middle Aged, United States, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin, Ethnicity, Racial Groups, White", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"39447981\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Wellbeing,Emotional Processing,Spirituality,Observational Study", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3106, "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 F, Roseman L, Mediano P, Timmermann C, Oestreich L, Pagni B, Zeifman R, Hampshire A, Trender W, Douglass H, Girn M, Godfrey K, Kettner H, Sharif F, Espasiano L, Gazzaley A, Wall M, Erritzoe D, Nutt D, Carhart-Harris R.", "abstract": "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 unknown. In a placebo-controlled, within-subjects, electroencephalography, and magnetic resonance imaging study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes were 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 were seen at one-month. Diffusion imaging done before and one-month after 25mg psilocybin revealed decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlated with decreased brain network modularity over the same time period. Decreased modularity also correlated with improved well-being. Increased cortical signal entropy at 1- and 2-hours post-dosing predicted improved psychological well-being at one-month. Next-day psychological insight mediated the entropy to well-being relationship. All effects were exclusive to 25mg psilocybin; no effects occurred with a 1mg psilocybin ‘placebo’ dose.", "journal": "bioRxiv", "publication_date": "2024-10-13", "publication_year": 2024, "doi": "10.1101/2024.10.11.617955", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2024.10.11.617955", "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\":\"PPR924123\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Aging,Wellbeing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 997, "title": "Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial.", "normalized_title": "effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate to severe major depressive disorder observational 6 month follow up of a phase 2 double blind randomised controlled trial", "authors": "Erritzoe D, Barba T, Greenway KT, Murphy R, Martell J, Giribaldi B, Timmermann C, Murphy-Beiner A, Jones MB, Nutt D, Weiss B, Carhart-Harris R.", "abstract": "BackgroundPsilocybin therapy (PT) produces rapid and persistent antidepressant effects in major depressive disorder (MDD). However, the long-term effects of PT have never been compared with gold-standard treatments for MDD such as pharmacotherapy or psychotherapy alone or in combination.MethodsThis is a 6-month follow-up study of a phase 2, double-blind, randomised, controlled trial involving patients with moderate-to-severe MDD. Participants were recruited from a hospital in the UK. Male or female patients with major depressive disorder (DSM-IV), moderate to severe depression (HAM-D ≥17), no MRI or SSRI contraindications, confirmed diagnosis by a GP or mental healthcare professional, aged 18-80, and competent in English were eligible. Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support ('psilocybin therapy' or PT) and book-ended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support ('escitalopram treatment' or ET). The primary outcome measure was change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) at week 6, which has been reported previously. Herein, we present results at the 6-month follow-up time point. Measures of social functioning, connectedness, and meaning in life constituted the study's secondary outcomes during follow-up. Safety in the follow-up period was not assessed. This trial is registered at ClinicalTrials.gov, NCT03429075.FindingsBetween January 15th, 2019 and March 20th, 2020, 59 patients were enrolled and 30 (11 females [37%] and 19 males [63%]) were assigned to the psilocybin group and 29 (9 females [31%] and 20 males [69%]) to the escitalopram group. 25 participants in the PT group and 21 in the ET group completed the 6-month follow-up. At the 6-month follow-up, both PT and ET conditions yielded sustained improvements in depressive symptom severity. The mean between-condition difference in QIDS-SR-16 scores at 6-months was 1.51 (95% CI: -1.35, 4.38; p = 0.311). Secondary outcomes demonstrated that PT had greater mean between-condition differences in functioning (WSAS: -7.46; 95% CI: -12.4, -2.47; p", "journal": null, "publication_date": "2024-09-20", "publication_year": 2024, "doi": "10.1016/j.eclinm.2024.102799", "pubmed_id": "39764567", "source_url": "https://doi.org/10.1016/j.eclinm.2024.102799", "keywords": "", "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\":\"39764567\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Receptor Pharmacology,Clinical Trial,Observational Study,Safety,Contraindications", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1046, "title": "Within-subject comparison of near-death and psychedelic experiences: acute and enduring effects.", "normalized_title": "within subject comparison of near death and psychedelic experiences acute and enduring effects", "authors": "Martial C, Carhart-Harris R, Timmermann C.", "abstract": "Mystical-like states of consciousness may arise through means such as psychedelic substances, but may also occur unexpectedly during near-death experiences (NDEs). So far, research studies comparing experiences induced by serotonergic psychedelics and NDEs, along with their enduring effects, have employed between-subject designs, limiting direct comparisons. We present results from an online survey exploring the phenomenology, attribution of reality, psychological insights, and enduring effects of NDEs and psychedelic experiences (PEs) in individuals who have experienced both at some point during their lifetime. We used frequentist and Bayesian analyses to determine significant differences and overlaps (evidence for null hypotheses) between the two. Thirty-one adults reported having experienced both an NDE (i.e. NDE-C scale total score ≥27/80) and a PE (intake of lysergic acid diethylamide, psilocybin/mushrooms, ayahuasca, N,N-dimethyltryptamine, or mescaline). Results revealed areas of overlap between both experiences for phenomenology, attribution of reality, psychological insights, and enduring effects. A finer-grained analysis of the phenomenology revealed a significant overlap in mystical-like effects, while low-level phenomena (sensory effects) were significantly different, with NDEs displaying higher scores of disembodiment and PEs higher scores of visual imagery. This suggests psychedelics as a useful model for studying mystical-like effects induced by NDEs, while highlighting distinctions in sensory experiences.", "journal": null, "publication_date": "2024-08-29", "publication_year": 2024, "doi": "10.1093/nc/niae033", "pubmed_id": "39220326", "source_url": "https://doi.org/10.1093/nc/niae033", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"39220326\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,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" }, { "id": 3268, "title": "A virtual clinical trial of psychedelics to treat patients with disorders of consciousness", "normalized_title": "a virtual clinical trial of psychedelics to treat patients with disorders of consciousness", "authors": "Alnagger NL, Cardone P, Martial C, Sanz Perl Y, Mindlin I, Sitt JD, Roseman L, Carhart-Harris R, Nutt D, Mallaroni P, Mason NL, Ramaekers JG, Bonhomme V, Laureys S, Deco G, Gosseries O, Nunez P, Annen J.", "abstract": "Disorders of consciousness (DoC), including the unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), have limited treatment options. Recent research suggests that psychedelic drugs, known for their complexity-enhancing properties, could be promising treatments for DoC. This study uses whole-brain computational models to explore this potential. We created individualised models for DoC patients, optimised with empirical fMRI and diffusion-weighted imaging (DWI) data, and simulated the administration of LSD and psilocybin. We used an in-silico perturbation protocol to distinguish between different states of consciousness, including DoC, anaesthesia, and the psychedelic state, and assess the dynamical stability of the brains of DoC patients pre- and post-psychedelic simulation. Our findings indicate that LSD and psilocybin shift DoC patients' brains closer to criticality, with a greater effect in MCS patients. In UWS patients, the treatment response correlates with structural connectivity, while in MCS patients, it aligns with baseline functional connectivity. This virtual clinical trial lays a computational foundation for using psychedelics in DoC treatment and highlights the future role of computational modelling in drug discovery and personalised medicine.", "journal": "bioRxiv", "publication_date": "2024-08-18", "publication_year": 2024, "doi": "10.1101/2024.08.16.608251", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2024.08.16.608251", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR897826\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Consciousness,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" }, { "id": 1074, "title": "Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy.", "normalized_title": "longitudinal experiences of canadians receiving compassionate access to psilocybin assisted psychotherapy", "authors": "de la Salle S, Kettner H, Thibault Lévesque J, Garel N, Dames S, Patchett-Marble R, Rej S, Gloeckler S, Erritzoe D, Carhart-Harris R, Greenway KT.", "abstract": "Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these 'real-world' patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.", "journal": null, "publication_date": "2024-07-16", "publication_year": 2024, "doi": "10.1038/s41598-024-66817-0", "pubmed_id": "39019922", "source_url": "https://doi.org/10.1038/s41598-024-66817-0", "keywords": "Humans, Hallucinogens, Longitudinal Studies, Prospective Studies, Depression, Anxiety, Psychotherapy, Quality of Life, Adult, Aged, Middle Aged, Canada, Female, Male, Compassionate Use Trials, Psilocybin, North American People", "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\":\"39019922\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,End-of-Life Distress,Chronic Pain,Mechanism of Action,Wellbeing,Spirituality,Clinical Trial,Observational Study", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1058, "title": "Psilocybin desynchronizes the human brain.", "normalized_title": "psilocybin desynchronizes the human brain", "authors": "Siegel JS, Subramanian S, Perry D, Kay BP, Gordon EM, Laumann TO, Reneau TR, Metcalf NV, Chacko RV, Gratton C, Horan C, Krimmel SR, Shimony JS, Schweiger JA, Wong DF, Bender DA, Scheidter KM, Whiting FI, Padawer-Curry JA, Shinohara RT, Chen Y, Moser J, Yacoub E, Nelson SM, Vizioli L, Fair DA, Lenze EJ, Carhart-Harris R, Raison CL, Raichle ME, Snyder AZ, Nicol GE, Dosenbach NUF.", "abstract": "A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.", "journal": null, "publication_date": "2024-07-16", "publication_year": 2024, "doi": "10.1038/s41586-024-07624-5", "pubmed_id": "39020167", "source_url": "https://doi.org/10.1038/s41586-024-07624-5", "keywords": "Brain, Hippocampus, Nerve Net, Humans, Methylphenidate, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Ego, Space Perception, Time Perception, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Healthy Volunteers, Psilocybin, Default Mode Network", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"39020167\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,Brain Imaging,Default Mode Network,Aging,Clinical Trial,Animal Study,Healthy Volunteers,Adolescents", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1111, "title": "Study protocol for \"Psilocybin in patients with fibromyalgia: brain biomarkers of action\".", "normalized_title": "study protocol for psilocybin in patients with fibromyalgia brain biomarkers of action", "authors": "Bornemann J, Close JB, Ahmad K, Barba T, Godfrey K, Macdonald L, Erritzoe D, Nutt D, Carhart-Harris R.", "abstract": "BackgroundChronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI).MethodsTwenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity - plus event-related potential functional plasticity markers, captured via EEG.DiscussionThe results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic action of psychedelic-therapy more broadly. It will also deliver essential data to inform the design of a potential subsequent RCT.", "journal": null, "publication_date": "2024-06-03", "publication_year": 2024, "doi": "10.3389/fpsyt.2024.1320780", "pubmed_id": "38983371", "source_url": "https://doi.org/10.3389/fpsyt.2024.1320780", "keywords": "", "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\":\"38983371\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Chronic Pain,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Randomized Controlled Trial,Observational Study", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "id": 1145, "title": "Psychedelics and the 'inner healer': Myth or mechanism?", "normalized_title": "psychedelics and the inner healer myth or mechanism", "authors": "Peill J, Marguilho M, Erritzoe D, Barba T, Greenway KT, Rosas F, Timmermann C, Carhart-Harris R.", "abstract": "BackgroundReference to an intrinsic healing mechanism or an 'inner healer' is commonplace amongst psychedelic drug-using cultures. The 'inner healer' refers to the belief that psychedelic compounds, plants or concoctions have an intrinsically regenerative action on the mind and brain, analogous to intrinsic healing mechanisms within the physical body, for example, after sickness or injury.AimsHere, we sought to test and critique this idea by devising a single subjective rating item pertaining to perceived 'inner healing' effects.MethodsThe item was issued to 59 patients after a single high (25 mg, n = 30) or 'placebo' (1 mg, n = 29) dose of psilocybin in a double-blind randomised controlled trial of psilocybin for depression.ResultsInner healer scores were higher after the high versus placebo dose of psilocybin (t = 3.88, p", "journal": null, "publication_date": "2024-04-11", "publication_year": 2024, "doi": "10.1177/02698811241239206", "pubmed_id": "38605658", "source_url": "https://doi.org/10.1177/02698811241239206", "keywords": "Humans, Hallucinogens, Double-Blind Method, Depression, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"38605658\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,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": "published" }, { "id": 1148, "title": "Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression.", "normalized_title": "effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression", "authors": "Erritzoe D, Barba T, Spriggs MJ, Rosas FE, Nutt DJ, Carhart-Harris R.", "abstract": "BackgroundThere is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling.AimsUsing data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes.MethodsExploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored.Results/outcomesIn the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found.ConclusionDiscontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.", "journal": null, "publication_date": "2024-03-21", "publication_year": 2024, "doi": "10.1177/02698811241237870", "pubmed_id": "38520045", "source_url": "https://doi.org/10.1177/02698811241237870", "keywords": "Humans, Hallucinogens, Treatment Outcome, Drug Therapy, Combination, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"38520045\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Receptor Pharmacology,Wellbeing,Clinical Trial,Safety,Drug Interactions", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1135, "title": "Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity.", "normalized_title": "predicting the outcome of psilocybin treatment for depression from baseline fmri functional connectivity", "authors": "Copa D, Erritzoe D, Giribaldi B, Nutt D, Carhart-Harris R, Tagliazucchi E.", "abstract": "BackgroundPsilocybin is a serotonergic psychedelic drug under assessment as a potential therapy for treatment-resistant and major depression. Heterogeneous treatment responses raise interest in predicting the outcome from baseline data.MethodsA machine learning pipeline was implemented to investigate baseline resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI) as a predictor of symptom severity in psilocybin monotherapy for treatment-resistant depression (16 patients administered two 5 mg capsules followed by 25 mg, separated by one week). Generalizability was tested in a sample of 22 patients who participated in a psilocybin vs. escitalopram trial for moderate-to-severe major depression (two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo vs. two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram). The analysis was repeated using both samples combined.ResultsFunctional connectivity of visual, default mode and executive networks predicted early symptom improvement, while the salience network predicted responders up to 24 weeks after treatment (accuracy≈0.9). Generalization performance was borderline significant. Consistent results were obtained from the combined sample analysis. Fronto-occipital and fronto-temporal coupling predicted early and late symptom reduction, respectively.LimitationsThe number of participants and differences between the two datasets limit the generalizability of the findings, while the lack of a placebo arm limits their specificity.ConclusionsBaseline neurophysiological measurements can predict the outcome of psilocybin treatment for depression. Future research based on larger datasets should strive to assess the generalizability of these predictions.", "journal": null, "publication_date": "2024-02-26", "publication_year": 2024, "doi": "10.1016/j.jad.2024.02.089", "pubmed_id": "38423367", "source_url": "https://doi.org/10.1016/j.jad.2024.02.089", "keywords": "Humans, Magnetic Resonance Imaging, Depression, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"38423367\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Aging,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "id": 1224, "title": "Brain dynamics predictive of response to psilocybin for treatment-resistant depression.", "normalized_title": "brain dynamics predictive of response to psilocybin for treatment resistant depression", "authors": "Vohryzek J, Cabral J, Lord LD, Fernandes HM, Roseman L, Nutt DJ, Carhart-Harris RL, Deco G, Kringelbach ML.", "abstract": "Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here, we leveraged the differential outcome in responders and non-responders to psilocybin (10 and 25 mg, 7 days apart) therapy for depression-to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a healthy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-hydroxytryptamine 2a and 5-hydroxytryptamine 1a, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression, and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.", "journal": null, "publication_date": "2024-02-14", "publication_year": 2024, "doi": "10.1093/braincomms/fcae049", "pubmed_id": "38515439", "source_url": "https://doi.org/10.1093/braincomms/fcae049", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"38515439\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1233, "title": "Effects of DMT on mental health outcomes in healthy volunteers.", "normalized_title": "effects of dmt on mental health outcomes in healthy volunteers", "authors": "Timmermann C, Zeifman RJ, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin's acute effects (4-6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via 'Oceanic Boundlessness'). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.", "journal": null, "publication_date": "2024-02-06", "publication_year": 2024, "doi": "10.1038/s41598-024-53363-y", "pubmed_id": "38326357", "source_url": "https://doi.org/10.1038/s41598-024-53363-y", "keywords": "Humans, N,N-Dimethyltryptamine, Hallucinogens, Prospective Studies, Healthy Volunteers, Psilocybin, Outcome Assessment, Health Care", "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\":\"38326357\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Wellbeing,Observational Study,Healthy Volunteers", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1231, "title": "Psychedelics and sexual functioning: a mixed-methods study.", "normalized_title": "psychedelics and sexual functioning a mixed methods study", "authors": "Barba T, Kettner H, Radu C, Peill JM, Roseman L, Nutt DJ, Erritzoe D, Carhart-Harris R, Giribaldi B.", "abstract": "Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake inhibitors (SSRIs), a first line treatment for depression. The aim of the present paper was to investigate the post-acute effects of psychedelics on self-reported sexual functioning, combining data from two independent studies, one large and naturalistic and the other a smaller but controlled clinical trial. Naturalistic use of psychedelics was associated with improvements in several facets of sexual functioning and satisfaction, including improved pleasure and communication during sex, satisfaction with one's partner and physical appearance. Convergent results were found in a controlled trial of psilocybin therapy versus an SSRI, escitalopram, for depression. In this trial, patients treated with psilocybin reported positive changes in sexual functioning after treatment, while patients treated with escitalopram did not. Despite focusing on different populations and settings, this is the first research study to quantitively investigate the effects of psychedelics on sexual functioning. Results imply a potential positive effect on post-acute sexual functioning and highlight the need for more research on this.", "journal": null, "publication_date": "2024-02-06", "publication_year": 2024, "doi": "10.1038/s41598-023-49817-4", "pubmed_id": "38326446", "source_url": "https://doi.org/10.1038/s41598-023-49817-4", "keywords": "Humans, Hallucinogens, Sexual Behavior, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"38326446\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Receptor Pharmacology,Wellbeing,Clinical Trial,Adverse Events", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1122, "title": "Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression.", "normalized_title": "assessing expectancy and suggestibility in a trial of escitalopram v psilocybin for depression", "authors": "Szigeti B, Weiss B, Rosas FE, Erritzoe D, Nutt D, Carhart-Harris R.", "abstract": "BackgroundTo investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075).MethodsWe used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin.ResultsPatients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm.ConclusionsOverall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.", "journal": null, "publication_date": "2024-01-21", "publication_year": 2024, "doi": "10.1017/s0033291723003653", "pubmed_id": "38247730", "source_url": "https://doi.org/10.1017/s0033291723003653", "keywords": "Humans, Citalopram, Hallucinogens, Treatment Outcome, Suggestion, Double-Blind Method, Adult, Middle Aged, Female, Male, Anticipation, Psychological, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"38247730\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "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" }, { "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" }, { "id": 3188, "title": "Synergistic, Multi-level Understanding of Psychedelics: Three Systematic Reviews and Meta-analyses of Their Pharmacology, Neuroimaging and Phenomenology", "normalized_title": "synergistic multi level understanding of psychedelics three systematic reviews and meta analyses of their pharmacology neuroimaging and phenomenology", "authors": "Shinozuka K, Jerotic K, Mediano P, Zhao AT, Preller KH, Carhart-Harris R, Kringelbach ML.", "abstract": "Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: 1) subjective experience (phenomenology), 2) neuroimaging and 3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT2A, 5-HT2C, or D2 receptors, relative to the 5-HT1A receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.", "journal": "bioRxiv", "publication_date": "2023-10-06", "publication_year": 2023, "doi": "10.1101/2023.10.06.561183", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2023.10.06.561183", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR738055\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Addiction,Brain Imaging,Pharmacology,Receptor Pharmacology,Consciousness,Aging,Systematic Review,Review Article,Safety", "study_type": "Systematic Review", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3718, "title": "Psilocybin therapy for treatment resistant depression: prediction of clinical outcome by natural language processing.", "normalized_title": "psilocybin therapy for treatment resistant depression prediction of clinical outcome by natural language processing", "authors": "Dougherty RF, Clarke P, Atli M, Kuc J, Schlosser D, Dunlop BW, Hellerstein DJ, Aaronson ST, Zisook S, Young AH, Carhart-Harris R, Goodwin GM, Ryslik GA.", "abstract": "RationaleTherapeutic administration of psychedelics has shown significant potential in historical accounts and recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways' proprietary synthetic formulation of psilocybin, in participants with treatment-resistant depression.ObjectiveWhile the phase-IIb results are promising, the treatment works for a portion of the population and early prediction of outcome is a key objective as it would allow early identification of those likely to require alternative treatment.MethodsTranscripts were made from audio recordings of the psychological support session between participant and therapist 1 day post COMP360 administration. A zero-shot machine learning classifier based on the BART large language model was used to compute two-dimensional sentiment (valence and arousal) for the participant and therapist from the transcript. These scores, combined with the Emotional Breakthrough Index (EBI) and treatment arm were used to predict treatment outcome as measured by MADRS scores. (Code and data are available at https://github.com/compasspathways/Sentiment2D.) RESULTS: Two multinomial logistic regression models were fit to predict responder status at week 3 and through week 12. Cross-validation of these models resulted in 85% and 88% accuracy and AUC values of 88% and 85%.ConclusionsA machine learning algorithm using NLP and EBI accurately predicts long-term patient response, allowing rapid prognostication of personalized response to psilocybin treatment and insight into therapeutic model optimization. Further research is required to understand if language data from earlier stages in the therapeutic process hold similar predictive power.", "journal": null, "publication_date": "2023-08-21", "publication_year": 2023, "doi": "10.1007/s00213-023-06432-5", "pubmed_id": "37606733", "source_url": "https://doi.org/10.1007/s00213-023-06432-5", "keywords": "Humans, Hallucinogens, Treatment Outcome, Double-Blind Method, Natural Language Processing, Adult, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant, Machine Learning, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:08:40", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"37606733\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Emotional Processing,Clinical Trial,Treatment-Resistant Depression,Safety", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1407, "title": "Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences.", "normalized_title": "co use of mdma with psilocybin lsd may buffer against challenging experiences and enhance positive experiences", "authors": "Zeifman RJ, Kettner H, Pagni BA, Mallard A, Roberts DE, Erritzoe D, Ross S, Carhart-Harris RL.", "abstract": "Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium-high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose-response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments.", "journal": null, "publication_date": "2023-08-21", "publication_year": 2023, "doi": "10.1038/s41598-023-40856-5", "pubmed_id": "37608057", "source_url": "https://doi.org/10.1038/s41598-023-40856-5", "keywords": "Humans, Methamphetamine, Hallucinogens, Prospective Studies, Fear, 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\":\"37608057\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Mystical Experience,Safety", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1390, "title": "Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: A systematic review and individual participant data meta-analysis.", "normalized_title": "assessing the risk of symptom worsening in psilocybin assisted therapy for depression a systematic review and individual participant data meta analysis", "authors": "Simonsson O, Carlbring P, Carhart-Harris R, Davis AK, Nutt DJ, Griffiths RR, Erritzoe D, Goldberg SB.", "abstract": "We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies.", "journal": null, "publication_date": "2023-07-22", "publication_year": 2023, "doi": "10.1016/j.psychres.2023.115349", "pubmed_id": "37523886", "source_url": "https://doi.org/10.1016/j.psychres.2023.115349", "keywords": "Humans, Hallucinogens, Sample Size, Depression, Symptom Flare Up, Psilocybin, Escitalopram", "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\":\"37523886\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Meta-Analysis,Systematic Review,Review Article,Safety", "study_type": "Meta-Analysis", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "id": 1464, "title": "In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape.", "normalized_title": "in vivo mapping of pharmacologically induced functional reorganization onto the human brain s neurotransmitter landscape", "authors": "Luppi AI, Hansen JY, Adapa R, Carhart-Harris RL, Roseman L, Timmermann C, Golkowski D, Ranft A, Ilg R, Jordan D, Bonhomme V, Vanhaudenhuyse A, Demertzi A, Jaquet O, Bahri MA, Alnagger NLN, 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 reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, 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 reorganization of the brain's functional architecture.", "journal": null, "publication_date": "2023-06-13", "publication_year": 2023, "doi": "10.1126/sciadv.adf8332", "pubmed_id": "37315149", "source_url": "https://doi.org/10.1126/sciadv.adf8332", "keywords": "Brain, Humans, Methylphenidate, Ketamine, Membrane Transport Proteins, Modafinil", "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\":\"37315149\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "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" }, { "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" }, { "id": 1295, "title": "Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression.", "normalized_title": "personality change in a trial of psilocybin therapy v escitalopram treatment for depression", "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": "BackgroundPsilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.MethodsIn a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.ResultsPT was associated with decreases in neuroticism (B = -0.63), introversion (B = -0.38), disagreeableness (B = -0.47), impulsivity (B = -0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = -0.47) and disagreeableness (B = -0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = -0.38), disagreeableness (B = -0.26), impulsivity (B = -0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = -0.46) remaining decreased at month 6. No significant between-condition differences were observed.ConclusionsPersonality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.", "journal": null, "publication_date": "2023-06-01", "publication_year": 2023, "doi": "10.1017/s0033291723001514", "pubmed_id": "37264814", "source_url": "https://doi.org/10.1017/s0033291723001514", "keywords": "Humans, Depression, Personality, Psilocybin, Neuroticism, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"37264814\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Personality Change,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "id": 1422, "title": "How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change.", "normalized_title": "how does psilocybin therapy work an exploration of experiential avoidance as a putative mechanism of change", "authors": "Zeifman RJ, Wagner AC, Monson CM, Carhart-Harris RL.", "abstract": "BackgroundPsilocybin therapy is receiving attention as a mental health intervention with transdiagnostic potential. In line with psychotherapeutic research, qualitative research has highlighted the role of reductions in experiential avoidance (and increases in connectedness) within psilocybin therapy. However, no quantitative research has examined experiential avoidance as a mechanism underlying psilocybin therapy's therapeutic effects.MethodData was used from a double-blind randomized controlled trial that compared psilocybin therapy (two 25 mg psilocybin session plus daily placebo for six weeks) with escitalopram (two 1 mg psilocybin sessions plus 10-20 mg daily escitalopram for six weeks) among individuals with major depressive disorder (N = 59). All participants received psychological support. Experiential avoidance, connectedness, and treatment outcomes were measured at pre-treatment and at a 6 week primary endpoint. Acute psilocybin experiences and psychological insight were also measured.ResultsWith psilocybin therapy, but not escitalopram, improvements in mental health outcomes (i.e., well-being, depression severity, suicidal ideation, and trait anxiety) occurred via reductions in experiential avoidance. Exploratory analyses suggested that improvements in mental health (except for suicidal ideation) via reduction in experiential avoidance were serially mediated through increases in connectedness. Additionally, experiences of ego dissolution and psychological insight predicted reductions in experiential avoidance following psilocybin therapy.LimitationsDifficulties inferring temporal causality, maintaining blindness to condition, and reliance upon self-report.ConclusionsThese results provide support for the role of reduced experiential avoidance as a putative mechanism underlying psilocybin therapy's positive therapeutic outcomes. The present findings may help to tailor, refine, and optimize psilocybin therapy and its delivery.", "journal": null, "publication_date": "2023-05-02", "publication_year": 2023, "doi": "10.1016/j.jad.2023.04.105", "pubmed_id": "37146908", "source_url": "https://doi.org/10.1016/j.jad.2023.04.105", "keywords": "Humans, Treatment Outcome, Anxiety, Anxiety Disorders, Psilocybin, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"37146908\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Wellbeing,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": "published" }, { "id": 1449, "title": "A critical evaluation of QIDS-SR-16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression.", "normalized_title": "a critical evaluation of qids sr 16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression", "authors": "Weiss B, Erritzoe D, Giribaldi B, Nutt DJ, Carhart-Harris RL.", "abstract": "BackgroundIn a recent clinical trial examining the comparative efficacy of psilocybin therapy (PT) versus escitalopram treatment (ET) for major depressive disorder, 14 of 16 major efficacy outcome measures yielded results that favored PT, but the Quick Inventory of Depressive Symptomatology, Self-Report, 16 items (QIDS-SR16) did not.AimsThe present study aims to (1) rationally and psychometrically account for discrepant results between outcome measures and (2) to overcome psychometric problems particular to individual measures by re-examining between-condition differences in depressive response using all outcome measures at item-, facet-, and factor-levels of analysis.MethodFour depression measures were compared on the basis of their validity for examining differences in depressive response between PT and ET conditions.Results/outcomesPossible reasons for discrepant findings on the QIDS-SR16 include its higher variance, imprecision due to compound items and whole-scale and unidimensional sum-scoring, vagueness in the phrasing of scoring options for items, and its lack of focus on a core depression factor. Reanalyzing the trial data at item-, facet-, and factor-levels yielded results suggestive of PT's superior efficacy in reducing depressed mood, anhedonia, and a core depression factor, along with specific symptoms such as sexual dysfunction.Conclusion/interpretationOur results raise concerns about the adequacy of the QIDS-SR16 for measuring depression, as well as the practice of relying on individual scales that tend not to capture the multidimensional structure or core of depression. Using an alternative approach that captures depression more granularly and comprehensively yielded specific insight into areas where PT therapy may be particularly useful to patients and clinicians.", "journal": null, "publication_date": "2023-04-24", "publication_year": 2023, "doi": "10.1177/02698811231167848", "pubmed_id": "37122239", "source_url": "https://doi.org/10.1177/02698811231167848", "keywords": "Humans, Reproducibility of Results, Depression, Psychiatric Status Rating Scales, Clinical Trials as Topic, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"37122239\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Clinical Trial,Healthcare Workers", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1429, "title": "Increased low-frequency brain responses to music after psilocybin therapy for depression.", "normalized_title": "increased low frequency brain responses to music after psilocybin therapy for depression", "authors": "Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RL.", "abstract": "BackgroundPsychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following PT.MethodsBrain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of psilocybin dosing sessions.ResultsComparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions.LimitationsOpen-label trial. Relatively small sample size.ConclusionsThese data suggest an effect of PT on the brain's response to music, implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.", "journal": null, "publication_date": "2023-04-22", "publication_year": 2023, "doi": "10.1016/j.jad.2023.04.081", "pubmed_id": "37094657", "source_url": "https://doi.org/10.1016/j.jad.2023.04.081", "keywords": "Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Depression, Music, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"37094657\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Aging,Emotional Processing,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1594, "title": "Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness.", "normalized_title": "among psychedelic experienced users only past use of psilocybin reliably predicts nature relatedness", "authors": "Forstmann M, Kettner HS, Sagioglou C, Irvine A, Gandy S, Carhart-Harris RL, Luke D.", "abstract": "BackgroundPast research reports a positive relationship between experience with classic serotonergic psychedelics and nature relatedness (NR). However, these studies typically do not distinguish between different psychedelic compounds, which have a unique psychopharmacology and may be used in specific contexts and with different intentions. Likewise, it is not clear whether these findings can be attributed to substance use per se or unrelated variables that differentiate psychedelic users from nonusers.AimsThe present study was designed to determine the relative degree to which lifetime experience with different psychedelic substances is predictive of self-reported NR among psychedelic-experienced users.MethodsWe conducted a combined reanalysis of five independent datasets (N = 3817). Using standard and regularized regression analyses, we tested the relationship between degree of experience with various psychedelic substances (binary and continuous) and NR, both within a subsample of psychedelic-experienced participants as well as the complete sample including psychedelic-naïve participants.Results/outcomesAmong people experienced with psychedelics, only past use of psilocybin (versus LSD, mescaline, Salvia divinorum, ketamine, and ibogaine) was a reliable predictor of NR and its subdimensions. Weaker, less reliable results were obtained for the pharmacologically similar N,N-dimethyltryptamine (DMT). Results replicate when including psychedelic-naïve participants. In addition, among people exclusively experience with psilocybin, use frequency positively predicted NR.Conclusions/interpretationResults suggest that experience with psilocybin is the only reliable (and strongest) predictor of NR. Future research should focus on psilocybin when investigating effects of psychedelic on NR and determine whether pharmacological attributes or differences in user expectations/use settings are responsible for this observation.", "journal": null, "publication_date": "2023-01-04", "publication_year": 2023, "doi": "10.1177/02698811221146356", "pubmed_id": "36601974", "source_url": "https://doi.org/10.1177/02698811221146356", "keywords": "Humans, N,N-Dimethyltryptamine, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"36601974\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Addiction,Pharmacology", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "id": 1600, "title": "Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression.", "normalized_title": "changes in music evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression", "authors": "Shukuroglou M, Roseman L, Wall M, Nutt D, Kaelen M, Carhart-Harris R.", "abstract": "BackgroundMusic listening is a staple and valued component of psychedelic therapy, and previous work has shown that psychedelics can acutely enhance music-evoked emotion.AimsThe present study sought to examine subjective responses to music before and after psilocybin therapy for treatment-resistant depression, while functional magnetic resonance imaging (fMRI) data was acquired.MethodsNineteen patients with treatment-resistant depression received a low oral dose (10 mg) of psilocybin, and a high dose (25 mg) 1 week later. fMRI was performed 1 week prior to the first dosing session and 1 day after the second. Two scans were conducted on each day: one with music and one without. Visual analogue scale ratings of music-evoked 'pleasure' plus ratings of other evoked emotions (21-item Geneva Emotional Music Scale) were completed after each scan. Given its role in musical reward, the nucleus accumbens (NAc) was chosen as region of interest for functional connectivity (FC) analyses. Effects of drug (vs placebo) and music (vs no music) on subjective and FC outcomes were assessed. Anhedonia symptoms were assessed pre- and post-treatment (Snaith-Hamilton Pleasure Scale).ResultsResults revealed a significant increase in music-evoked emotion following treatment with psilocybin that correlated with post-treatment reductions in anhedonia. A post-treatment reduction in NAc FC with areas resembling the default mode network was observed during music listening (vs no music).ConclusionThese results are consistent with current thinking on the role of psychedelics in enhancing music-evoked pleasure and provide some new insight into correlative brain mechanisms.", "journal": null, "publication_date": "2022-11-25", "publication_year": 2022, "doi": "10.1177/02698811221125354", "pubmed_id": "36433778", "source_url": "https://doi.org/10.1177/02698811221125354", "keywords": "Humans, Hallucinogens, Magnetic Resonance Imaging, Depression, Emotions, Music, Anhedonia, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"36433778\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Mechanism of Action,Default Mode Network,Aging,Emotional Processing,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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": null, "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": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"36373934\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "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" }, { "id": 1642, "title": "Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.", "normalized_title": "single dose psilocybin for a treatment resistant episode of major depression", "authors": "Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Páleníček T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E.", "abstract": "BackgroundPsilocybin is being studied for use in treatment-resistant depression.MethodsIn this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).ResultsA total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P", "journal": null, "publication_date": "2022-10-31", "publication_year": 2022, "doi": "10.1056/nejmoa2206443", "pubmed_id": "36322843", "source_url": "https://doi.org/10.1056/nejmoa2206443", "keywords": "Humans, Antidepressive Agents, Treatment Outcome, Double-Blind Method, Depression, Adult, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"36322843\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Clinical Trial,Treatment-Resistant Depression", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3730, "title": "A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression.", "normalized_title": "a bayesian reanalysis of a trial of psilocybin versus escitalopram for depression", "authors": "Nayak SM, Bari BA, Yaden DB, Spriggs MJ, Rosas FE, Peill JM, Giribaldi B, Erritzoe D, Nutt DJ, Carhart-Harris R.", "abstract": "ObjectivesTo perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis.DesignReanalysis of a two-arm double-blind placebo controlled trial.ParticipantsFifty-nine patients with MDD.InterventionsTwo doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups.Outcome measuresQuick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A.ResultsUsing Bayes factors and 'skeptical priors' which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a 'clinically meaningful amount' (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin's non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis.ConclusionsThis Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful--and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments.Trial registration numberNCT03429075.", "journal": null, "publication_date": "2022-10-27", "publication_year": 2022, "doi": "10.1089/psymed.2022.0002", "pubmed_id": "37337526", "source_url": "https://doi.org/10.1089/psymed.2022.0002", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:08:42", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"37337526\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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": null, "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": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"36192411\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "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" }, { "id": 1669, "title": "Effects of classic psychedelic drugs on turbulent signatures in brain dynamics.", "normalized_title": "effects of classic psychedelic drugs on turbulent signatures in brain dynamics", "authors": "Cruzat J, Perl YS, Escrichs A, Vohryzek J, Timmermann C, Roseman L, Luppi AI, Ibañez A, Nutt D, Carhart-Harris R, Tagliazucchi E, Deco G, Kringelbach ML.", "abstract": "Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, yet their mechanisms of action are not fully understood. A fundamental hypothesis is that psychedelics work by dose-dependently changing the functional hierarchy of brain dynamics, but it is unclear whether different psychedelics act similarly. Here, we investigated the changes in the brain's functional hierarchy associated with two different psychedelics (LSD and psilocybin). Using a novel turbulence framework, we were able to determine the vorticity, that is, the local level of synchronization, that allowed us to extend the standard global time-based measure of metastability to become a local-based measure of both space and time. This framework produced detailed signatures of turbulence-based hierarchical change for each psychedelic drug, revealing consistent and discriminate effects on a higher level network, that is, the default mode network. Overall, our findings directly support a prior hypothesis that psychedelics modulate (i.e., \"compress\") the functional hierarchy and provide a quantification of these changes for two different psychedelics. Implications for therapeutic applications of psychedelics are discussed.", "journal": null, "publication_date": "2022-09-30", "publication_year": 2022, "doi": "10.1162/netn_a_00250", "pubmed_id": "38800462", "source_url": "https://doi.org/10.1162/netn_a_00250", "keywords": "", "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\":\"38800462\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Mechanism of Action,Default Mode Network", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3244, "title": "Psilocybin Therapy for Treatment Resistant Depression: Prediction of Clinical Outcome by Natural Language Processing", "normalized_title": "psilocybin therapy for treatment resistant depression prediction of clinical outcome by natural language processing", "authors": "Dougherty RF, Clarke P, Alti M, Kuc J, Schlosser D, Dunlop BW, Hellerstein DJ, Aaronson ST, Zisook S, Young AH, Carhart-Harris R, Goodwin G, Ryslik GA.", "abstract": "Background: Therapeutic administration of psychedelic drugs has shown significant potential in historical accounts and in recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways’ proprietary synthetic formulation of psilocybin, in participants with treatment resistant depression. While promising, the treatment works for a portion of the population and early prediction of outcome is a key objective. Methods: Transcripts were made from audio recordings of the psychological support session between participant and therapist one day post COMP360 administration. A zero-shot machine learning classifier based on the BART large language model was used to compute two-dimensional sentiment (valence and arousal) for the participant and therapist from the transcript. These scores, combined with the Emotional Breakthrough Index (EBI) and treatment arm were used to predict treatment outcome as measured by MADRS scores. Code and data are available at https://github.com/compasspathways/Sentiment2DResults: Two multinomial logistic regression models were fit to predict responder status at week 3 and through week 12. Cross-validation of these models resulted in 85% and 88% accuracy and AUC values of 88% and 85%. Conclusions: A machine learning algorithm using NLP and EBI accurately predicts long term patient response, allowing rapid prognostication of personalized response to psilocybin treatment and insight into therapeutic model optimization. Further research is required to understand if language data from earlier stages in the therapeutic process hold similar predictive power.", "journal": "PsyArXiv", "publication_date": "2022-09-29", "publication_year": 2022, "doi": "10.31234/osf.io/kh3cx", "pubmed_id": null, "source_url": "https://doi.org/10.31234/osf.io/kh3cx", "keywords": "", "substance_tags": "psilocybin", "source_name": "PsyArXiv", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR553222\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"PsyArXiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Emotional Processing,Clinical Trial,Safety", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3126, "title": "Brain dynamics predictive of response to psilocybin for treatment-resistant depression", "normalized_title": "brain dynamics predictive of response to psilocybin for treatment resistant depression", "authors": "Vohryzek J, Cabral J, Lord L, Fernandes H, Roseman L, Nutt D, Carhart-Harris R, Deco G, Kringelbach M.", "abstract": "Abstract Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (> 50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.", "journal": "Research Square", "publication_date": "2022-09-19", "publication_year": 2022, "doi": "10.21203/rs.3.rs-2060381/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-2060381/v1", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR548038\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1698, "title": "Effects of psilocybin versus escitalopram on rumination and thought suppression in depression.", "normalized_title": "effects of psilocybin versus escitalopram on rumination and thought suppression in depression", "authors": "Barba T, Buehler S, Kettner H, Radu C, Cunha BG, Nutt DJ, Erritzoe D, Roseman L, Carhart-Harris R.", "abstract": "BackgroundMajor depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression.AimsTo assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder.MethodBased on data derived from a randomised clinical trial (N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction.ResultsA time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight.ConclusionsThese data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.", "journal": null, "publication_date": "2022-09-05", "publication_year": 2022, "doi": "10.1192/bjo.2022.565", "pubmed_id": "36065128", "source_url": "https://doi.org/10.1192/bjo.2022.565", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"36065128\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Drug Interactions", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1651, "title": "The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world.", "normalized_title": "the watts connectedness scale a new scale for measuring a sense of connectedness to self others and world", "authors": "Watts R, Kettner H, Geerts D, Gandy S, Kartner L, Mertens L, Timmermann C, Nour MM, Kaelen M, Nutt D, Carhart-Harris R, Roseman L.", "abstract": "RationaleA general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of 'connectedness' as 'a state of feeling connected to self, others and the wider world'. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as 'social connectedness' or 'nature connectedness', which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to 'self', 'others' and 'world' and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use.ObjectivesTo validate and test the 'Watts Connectedness Scale' (WCS).MethodsPsychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint.ResultsAs hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant post-psychedelic increases were observed for total connectedness scores (η2 = 0.339, p", "journal": null, "publication_date": "2022-08-07", "publication_year": 2022, "doi": "10.1007/s00213-022-06187-5", "pubmed_id": "35939083", "source_url": "https://doi.org/10.1007/s00213-022-06187-5", "keywords": "Humans, Hallucinogens, Emotions, Surveys and Questionnaires, Psilocybin, 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\":\"35939083\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Emotional Processing,Clinical Trial,Randomized Controlled Trial,Observational Study", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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" }, { "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" }, { "id": 3785, "title": "From Relaxed Beliefs Under Psychedelics (REBUS) to Revised Beliefs After Psychedelics (REBAS): Preliminary Development of the RElaxed Beliefs Questionnaire (REB-Q)", "normalized_title": "from relaxed beliefs under psychedelics rebus to revised beliefs after psychedelics rebas preliminary development of the relaxed beliefs questionnaire reb q", "authors": "Zeifman R, Spriggs MJ, Kettner H, Lyons T, Rosas F, Mediano P, Erritzoe D, Carhart-Harris R.", "abstract": "Background: The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs, and offers a unified account of the acute and therapeutic action of psychedelics. Although REBUS has received some neuroscientific support, little research has examined its psychological validity. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; (b) this relaxation and revision facilitates positive therapeutic outcomes and is associated with the entropy of EEG signals (an index of neurophysiological mechanisms relevant to REBUS). Method: Healthy individuals (N=11) were administered 1 mg and 25 mg psilocybin 4-weeks apart. Confidence ratings for personally held negative and positive beliefs were obtained before, during, and 4-weeks after dosing sessions. Acute entropy and self-reported subjective experiences were measured, as was well-being (before and 4-weeks after dosing sessions). Results: Confidence in negative self-beliefs decreased following 25 mg psilocybin and not following 1 mg psilocybin. Entropy and subjective effects under 25 mg psilocybin correlated with decreases in negative self-belief confidence (acute and 4-weeks after dosing). Particularly strong evidence was seen for a relationship between decreases in negative self-belief confidence and increases in well-being at 4-weeks. Conclusions: We report the first empirical evidence that the relaxation and revision of negative self-belief confidence mediates positive psychological outcomes; a psychological assumption of REBUS. Replication within larger and clinical samples remains necessary. We also introduce a new measure, the Relaxed BEliefs Questionnaire (REB-Q), for examining the robustness of these preliminary findings and the utility of the REBUS model.", "journal": "PsyArXiv", "publication_date": "2022-07-06", "publication_year": 2022, "doi": "10.31234/osf.io/w8j6t", "pubmed_id": null, "source_url": "https://doi.org/10.31234/osf.io/w8j6t", "keywords": "", "substance_tags": "psilocybin", "source_name": "PsyArXiv", "date_added": "2026-07-01 11:10:22", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"PPR515142\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"PsyArXiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Mechanism of Action,Wellbeing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3131, "title": "Brain dynamics predictive of response to psilocybin for treatment-resistant depression", "normalized_title": "brain dynamics predictive of response to psilocybin for treatment resistant depression", "authors": "Vohryzek J, Cabral J, Lord L, Fernandes HM, Roseman L, Nutt DJ, Carhart-Harris RL, Deco G, Kringelbach ML.", "abstract": "Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.", "journal": "bioRxiv", "publication_date": "2022-07-03", "publication_year": 2022, "doi": "10.1101/2022.06.30.497950", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2022.06.30.497950", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR521801\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3731, "title": "Psychedelic resting-state neuroimaging: A review and perspective on balancing replication and novel analyses.", "normalized_title": "psychedelic resting state neuroimaging a review and perspective on balancing replication and novel analyses", "authors": "McCulloch DE, Knudsen GM, Barrett FS, Doss MK, Carhart-Harris RL, Rosas FE, Deco G, Kringelbach ML, Preller KH, Ramaekers JG, Mason NL, Müller F, Fisher PM", "abstract": "Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology. We offer guidelines for future studies that encourage coherence in the field. Psychedelic rs-fMRI will benefit from the development of novel methods that expand our understanding of the brain mechanisms mediating its intriguing effects; yet, this field is at a crossroads where we must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics.", "journal": "Neuroscience and biobehavioral reviews", "publication_date": "2022-06-30", "publication_year": 2022, "doi": "10.1016/j.neubiorev.2022.104689", "pubmed_id": "35588933", "source_url": "https://pubmed.ncbi.nlm.nih.gov/35588933/", "keywords": "Ayahausca, Clinical, DMT, Entheogen, FMRI, Hallucinogen, Human, LSD, Neuroimaging, Psilocin, Psilocybin, Psychedelic, Replication, Resting-state, Serotonin", "substance_tags": "psilocybin,psilocin", "source_name": "PubMed", "date_added": "2026-07-01 11:08:43", "last_checked": "2026-07-01 11:20:39", "raw_json": "{\"pubmed_id\":\"35588933\"}", "topic_tags": "Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Review Article", "study_type": "Review Article", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3187, "title": "A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression", "normalized_title": "a bayesian reanalysis of a trial of psilocybin versus escitalopram for depression", "authors": "Nayak SM, Bari BA, Yaden DB, Spriggs MJ, Rosas F, Peill JM, Giribaldi B, Erritzoe D, Nutt D, Carhart-Harris R.", "abstract": "Objectives: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis. Design: Reanalysis of a two-arm double-blind placebo controlled trial.Participants: Fifty-nine patients with MDD.Interventions: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups.Outcome measures: Quick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A. Results: Using Bayes factors and ‘skeptical priors’ which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a ‘clinically meaningful amount’ (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin’s non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis. Conclusions: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful--and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments.", "journal": "PsyArXiv", "publication_date": "2022-06-30", "publication_year": 2022, "doi": "10.31234/osf.io/sb5ur", "pubmed_id": null, "source_url": "https://doi.org/10.31234/osf.io/sb5ur", "keywords": "", "substance_tags": "psilocybin", "source_name": "PsyArXiv", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR512763\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"PsyArXiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3770, "title": "A critique of: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds", "normalized_title": "a critique of skepticism about recent evidence that psilocybin opens depressed minds", "authors": "Carhart-Harris R, Daws RE, Nutt D.", "abstract": "This document details an authors' response to a critique of their work entitled: Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds.", "journal": "PsyArXiv", "publication_date": "2022-05-09", "publication_year": 2022, "doi": "10.31234/osf.io/pdbf5", "pubmed_id": null, "source_url": "https://doi.org/10.31234/osf.io/pdbf5", "keywords": "", "substance_tags": "psilocybin", "source_name": "PsyArXiv", "date_added": "2026-07-01 11:10:20", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR491363\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"PsyArXiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "General", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1727, "title": "Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex.", "normalized_title": "serotonergic psychedelic drugs lsd and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex", "authors": "Girn M, Roseman L, Bernhardt B, Smallwood J, Carhart-Harris R, Nathan Spreng R.", "abstract": "Lysergic acid diethylamide (LSD) and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. We applied a non-linear dimensionality reduction technique previously used to map hierarchical connectivity gradients to assess cortical organization in the LSD and psilocybin state from two previously published pharmacological resting-state fMRI datasets (N = 15 and 9, respectively). Results supported our primary hypothesis: The principal gradient of cortical connectivity, describing a hierarchy from unimodal to transmodal cortex, was significantly flattened under both drugs relative to their respective placebo conditions. Between-condition contrasts revealed that this was driven by a reduction of functional differentiation at both hierarchical extremes - default and frontoparietal networks at the upper end, and somatomotor at the lower. Gradient-based connectivity mapping indicated that this was underpinned by a disruption of modular unimodal connectivity and increased unimodal-transmodal crosstalk. Results involving the second and third gradient, which, respectively represent axes of sensory and executive differentiation, also showed significant alterations across both drugs. These findings provide support for a recent mechanistic model of the psychedelic state relevant to therapeutic applications of psychedelics. More fundamentally, we provide the first evidence that macroscale connectivity gradients are sensitive to an acute pharmacological manipulation, supporting a role for psychedelics as scientific tools to perturb cortical functional organization.", "journal": null, "publication_date": "2022-04-24", "publication_year": 2022, "doi": "10.1016/j.neuroimage.2022.119220", "pubmed_id": "35483649", "source_url": "https://doi.org/10.1016/j.neuroimage.2022.119220", "keywords": "Brain, Humans, Lysergic Acid Diethylamide, Serotonin Agents, Hallucinogens, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"35483649\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "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" }, { "id": 1798, "title": "Increased global integration in the brain after psilocybin therapy for depression.", "normalized_title": "increased global integration in the brain after psilocybin therapy for depression", "authors": "Daws RE, Timmermann C, Giribaldi B, Sexton JD, Wall MB, Erritzoe D, Roseman L, Nutt D, Carhart-Harris R.", "abstract": "Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Functional magnetic resonance imaging (fMRI) was recorded at baseline and 1 d after the 25-mg dose. Beck's depression inventory was the primary outcome measure ( MR/J00460X/1 ). The second trial was a double-blind phase II randomized controlled trial comparing psilocybin therapy with escitalopram. Patients with major depressive disorder received either 2 × 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo ('psilocybin arm') or 2 × 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) ('escitalopram arm'). fMRI was recorded at baseline and 3 weeks after the second psilocybin dose ( NCT03429075 ). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in fMRI brain network modularity, implying that psilocybin's antidepressant action may depend on a global increase in brain network integration. Network cartography analyses indicated that 5-HT2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after psilocybin treatment. The antidepressant response to escitalopram was milder and no changes in brain network organization were observed. Consistent efficacy-related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: global increases in brain network integration.", "journal": null, "publication_date": "2022-04-10", "publication_year": 2022, "doi": "10.1038/s41591-022-01744-z", "pubmed_id": "35411074", "source_url": "https://doi.org/10.1038/s41591-022-01744-z", "keywords": "Brain, Humans, Hallucinogens, Antidepressive Agents, Double-Blind Method, Depression, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"35411074\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Receptor Pharmacology,Aging,Clinical Trial,Randomized Controlled Trial,Treatment-Resistant Depression", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1802, "title": "Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression.", "normalized_title": "therapeutic alliance and rapport modulate responses to psilocybin assisted therapy for depression", "authors": "Murphy R, Kettner H, Zeifman R, Giribaldi B, Kartner L, Martell J, Read T, Murphy-Beiner A, Baker-Jones M, Nutt D, Erritzoe D, Watts R, Carhart-Harris R.", "abstract": "Background: Across psychotherapeutic frameworks, the strength of the therapeutic alliance has been found to correlate with treatment outcomes; however, its role has never been formally assessed in a trial of psychedelic-assisted therapy. We aimed to investigate the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes. Methods: This 2-arm double-blind randomized controlled trial compared escitalopram with psychedelic-assisted therapy for moderate-severe depressive disorder (N = 59). This analysis focused on the psilocybin condition (n = 30), who received two oral doses of 25 mg psilocybin, 3-weeks apart, with psychological preparation, in-session support, and integration therapy. A new psychedelic therapy model, called \"Accept-Connect-Embody\" (ACE), was developed in this trial. The primary outcome was depression severity 6 weeks post treatment (Quick Inventory of Depressive Symptomatology, QIDS-SR-16). Path analyses tested the hypothesis that therapeutic alliance (Scale To Assess the Therapeutic Relationship Patient Version, STAR-P) would predict depression outcomes via its influence on the acute psychedelic experience, specifically emotional-breakthrough (EBI) and mystical-type experiences (MEQ). The same analysis was performed on the escitalopram arm to test specificity. Results: The strength of therapeutic alliance predicted pre-session rapport, greater emotional-breakthrough and mystical-type experience (maximum EBI and MEQ scores across the two psilocybin sessions) and final QIDS scores (β = -0.22, R2 = 0.42 for EBIMax; β = -0.19, R2 = 0.32 for MEQMax). Exploratory path models revealed that final depression outcomes were more strongly affected by emotional breakthrough during the first, and mystical experience during the second session. Emotional breakthrough, but not mystical experience, during the first session had a positive effect on therapeutic alliance ahead of the second session (β = 0.79, p < 0.0001). Therapeutic alliance ahead of the second session had a direct impact on final depression scores, not mediated by the acute experience, with a weaker alliance ahead of the second psilocybin session predicting higher absolute depression scores at endpoint (β = -0.49, p < 0.001) Discussion: Future research could consider therapist training and characteristics; specific participant factors, e.g., attachment style or interpersonal trauma, which may underlie the quality of the therapeutic relationship, the psychedelic experience and clinical outcomes; and consider how therapeutic approaches might adapt in cases of weaker therapeutic alliance. Clinical Trial Registration: This trial is registered at http://clinicaltrials.gov, identifier (NCT03429075).", "journal": null, "publication_date": "2022-03-30", "publication_year": 2022, "doi": "10.3389/fphar.2021.788155", "pubmed_id": "35431912", "source_url": "https://doi.org/10.3389/fphar.2021.788155", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"35431912\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Emotional Processing,Mystical Experience,Clinical Trial,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": "published" }, { "id": 3227, "title": "Increased low-frequency brain responses to music after psilocybin therapy for depression", "normalized_title": "increased low frequency brain responses to music after psilocybin therapy for depression", "authors": "Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RL.", "abstract": "Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of the second of two psilocybin dosing sessions. Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Somewhat consistently, voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. These data suggest a specific effect of PT on the brain’s response to a hedonic stimulus (music), implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.", "journal": "bioRxiv", "publication_date": "2022-02-14", "publication_year": 2022, "doi": "10.1101/2022.02.13.480302", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2022.02.13.480302", "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\":\"PPR454661\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Aging,Emotional Processing,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1894, "title": "Study Protocol for \"Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study\".", "normalized_title": "study protocol for psilocybin as a treatment for anorexia nervosa a pilot study", "authors": "Spriggs MJ, Douglass HM, Park RJ, Read T, Danby JL, de Magalhães FJC, Alderton KL, Williams TM, Blemings A, Lafrance A, Nicholls DE, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present (1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and (2) a protocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin. Methods: (1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of \"recovery\" from the perspective of those with lived experience. (2) Protocol: Twenty female participants [21-65 years old, body mass index (BMI) 15 kg/m2 or above] will receive three oral doses of psilocybin (up to 25 mg) over a 6-week period delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our two-fold primary outcomes are (1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and (2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: (1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and (2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity. Discussion: The results of this pilot study will not only shed light on the acceptability, brain mechanisms, and impression of the potential efficacy of psilocybin as an adjunct treatment for AN but will be essential in shaping a subsequent Randomised Control Trial (RCT) that would test this treatment against a suitable control condition. Clinical Trial Registration: identifier: NCT04505189.", "journal": null, "publication_date": "2021-10-19", "publication_year": 2021, "doi": "10.3389/fpsyt.2021.735523", "pubmed_id": "34744825", "source_url": "https://doi.org/10.3389/fpsyt.2021.735523", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:06", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"34744825\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Eating Disorders,End-of-Life Distress,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Clinical Trial,Randomized Controlled Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" } ] }