{ "meta": { "tracker_site_url": "https://psilocybin-research.com", "publication_tracker_url": "https://psilocybin-research.com/", "generated_at_utc": "2026-07-02 18:46:56", "record_count": 43 }, "papers": [ { "id": 3002, "title": "Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits", "normalized_title": "modeled long term effects of psilocybin on dynamic activity and effective connectivity of fronto striatal thalamic circuits", "authors": "Pasquini Lorenzo, Vohryzek Jakub, Escrichs Anira, Perl Yonatan Sanz, Ponce-Alvarez Adrian, Idesis Sebastian, Girn Manesh, Roseman Leor, Mitchell Jennifer M., Gazzaley Adam, Kringelbach Morten, Nutt David J., Lyons Taylor, Carhart-Harris Robin L., Deco Gustavo", "abstract": "ABSTRACT Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we performed secondary analyses and applied computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first showed that dynamic FST activity increased 4 weeks after a full dose of psilocybin. We then proceeded to mechanistically account for these changes by providing tentative model-based support that reductions in the structure-function coupling contribute to increased dynamic FST activity postpsilocybin. Finally, we used computational approaches to show that psilocybin induces longitudinal increases in bottom-up and reduced top-down modulation of FST circuits. We then used publicly available receptor maps to show that cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, while increased information outflow via subcortical and limbic regions relates to local D2 receptor availability. Together, these findings suggest that increased FST flexibility weeks after a high dose of psilocybin is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism contributing to the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia nervosa.", "journal": "Human Brain Mapping", "publication_date": "2026-06-30", "publication_year": 2026, "doi": "10.1002/hbm.70596", "pubmed_id": null, "source_url": "https://doi.org/10.1002/hbm.70596", "keywords": "", "substance_tags": "psilocybin", "source_name": "Crossref", "date_added": "2026-07-01 11:03:06", "last_checked": "2026-07-02 06:54:51", "raw_json": "{\"doi\":\"10.1002/hbm.70596\",\"reference_dois\":[\"10.1146/annurev.neuro.9.1.357\",\"10.1016/j.bpsc.2022.04.003\",\"10.1016/j.jneumeth.2013.10.018\",\"10.1523/jneurosci.2830‐16.2016\",\"10.1001/jamapsychiatry.2022.2096\",\"10.1016/j.neuroimage.2017.03.045\",\"10.1016/j.celrep.2018.05.022.psychedelics\",\"10.1056/nejmoa2032994\",\"10.1016/s2215‐0366(16)30065‐7\",\"10.1073/pnas.1119598109\",\"10.1124/pr.118.017160\",\"10.1111/adb.12013\",\"10.1001/jamapsychiatry.2020.3285\",\"10.1038/s41591‐022‐01744‐z\",\"10.1016/j.celrep.2021.109836\",\"10.1016/j.cub.2018.07.083\",\"10.1073/pnas.1905534116\",\"10.1103/physreve.108.064410\",\"10.1038/s42003-022-03505-7\",\"10.1038/s41562-020-01003-6\",\"10.1016/j.nicl.2017.08.006\",\"10.1093/brain/awab406\",\"10.1038/s41398‐021‐01706‐y\",\"10.1073/pnas.2002509117\",\"10.1093/cercor/bhac064\",\"10.1101/306951\",\"10.1101/2025.04.22.650037\",\"10.1056/nejmoa2206443\",\"10.1016/j.neuroimage.2022.119671\",\"10.1016/j.nicl.2022.103233\",\"10.3109/00952990.2016.1170135\",\"10.1016/j.conb.2010.01.007\",\"10.1073/pnas.1921475117\",\"10.1016/j.celrep.2020.108128\",\"10.1126/sciadv.ade6049\",\"10.1038/s42003‐021‐02537‐9\",\"10.1038/s42003‐022‐03330‐y\",\"10.1038/s41467‐026‐71962‐3\",\"10.1016/j.euroneuro.2021.06.001\",\"10.1177/02698811211026454\",\"10.1038/s41586‐023‐06204‐3\",\"10.1124/pr.115.011478\",\"10.1073/pnas.1809298115\",\"10.1080/02791072.2017.1312643\",\"10.1177/0269881120909409\",\"10.1073/pnas.1815129116\",\"10.1371/journal.pcbi.1009139\",\"10.1016/j.neuron.2012.03.037\",\"10.1038/s41586‐024‐07624‐5\",\"10.1038/s41467‐019‐08934‐3\",\"10.1016/j.biopsych.2022.07.013\",\"10.1186/1477‐7525‐5‐63\",\"10.1006/nimg.2001.0978\",\"10.1126/science.adf0435\",\"10.1038/s41583‐020‐0367‐2\",\"10.1016/s0893‐133x(98)00108‐0\"],\"reference_count\":56}", "topic_tags": "Depression,Eating Disorders,Brain Imaging,Mechanism of Action,Receptor Pharmacology,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": 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": 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": 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": 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": 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": 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": 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": 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": 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": 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": 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": 1024, "title": "Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience.", "normalized_title": "co administration of midazolam and psilocybin differential effects on subjective quality versus memory of the psychedelic experience", "authors": "Nicholas CR, Banks MI, Lennertz RC, Wenthur CJ, Krause BM, Riedner BA, Smith RF, Hutson PR, Sauder CJ, Dunne JD, Roseman L, Raison CL.", "abstract": "Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.", "journal": null, "publication_date": "2024-09-11", "publication_year": 2024, "doi": "10.1038/s41398-024-03059-8", "pubmed_id": "39266503", "source_url": "https://doi.org/10.1038/s41398-024-03059-8", "keywords": "Humans, Midazolam, Hallucinogens, Memory, Adult, 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 11:22:01", "raw_json": "{\"europe_pmc_id\":\"39266503\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,Wellbeing,Healthy Volunteers", "study_type": "Other", "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": 3130, "title": "Co-administration of midazolam and psilocybin: Differential effects on subjective quality versus memory of the psychedelic experience", "normalized_title": "co administration of midazolam and psilocybin differential effects on subjective quality versus memory of the psychedelic experience", "authors": "Nicholas CR, Banks MI, Lennertz RL, Wenthur CJ, Krause BM, Riedner BA, Smith RF, Hutson PR, Sauder CJ, Dunne JD, Roseman L, Raison CL.", "abstract": "Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.", "journal": "bioRxiv", "publication_date": "2024-06-12", "publication_year": 2024, "doi": "10.1101/2024.06.13.598878", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2024.06.13.598878", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR867616\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Neuroplasticity,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": 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": 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": 1277, "title": "Is Poorly Assisted Psilocybin Treatment an Increasing Risk?", "normalized_title": "is poorly assisted psilocybin treatment an increasing risk", "authors": "Schenberg EE, King F, da Fonseca JE, Roseman L.", "abstract": "", "journal": null, "publication_date": "2023-12-31", "publication_year": 2023, "doi": "10.1176/appi.ajp.20230664", "pubmed_id": "38161296", "source_url": "https://doi.org/10.1176/appi.ajp.20230664", "keywords": "Humans, Lysergic Acid Diethylamide, Hallucinogens, Psychotherapy, Psilocybin", "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\":\"38161296\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Safety", "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": 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": 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": 1613, "title": "The Psychedelic Renaissance in Clinical Research: A Bibliometric Analysis of Three Decades of Human Studies with Psychedelics.", "normalized_title": "the psychedelic renaissance in clinical research a bibliometric analysis of three decades of human studies with psychedelics", "authors": "Hadar A, David J, Shalit N, Roseman L, Gross R, Sessa B, Lev-Ran S", "abstract": "Psychedelics were used in the treatment of psychiatric conditions prior to their prohibition in the late 1960s. In the past three decades, there is a revived research interest in the therapeutic potential of psychedelic drugs with expected FDA approvals for treatment of various conditions. Given the exponential scientific growth of this field, we sought to characterize, analyze, and visualize trends in its top-cited articles. Bibliometric analyses are quantitative approaches to characterize a scientific field, including evaluation of the impact of academic literature. The bibliometric analysis and visualizations were conducted with R-tools for comprehensive science mapping. The top-cited 100 articles were cited between 82 and 668 times (median 125; mean 158). Fifty-four percent of the T100 articles were produced in the past decade (2010-2020). Network and author impact analysis highlighted key figures and primary collaboration networks within the top 100 publications. UK, USA, Switzerland, Spain, and Brazil lead the field. Results are discussed in terms of research growth, access, diversity, and the distribution of knowledge and experience in the field. These aggregated data and insights on the second wave of psychedelic research facilitate research evaluation, data-driven funding policies, and a practical map for researchers and clinicians entering the field.", "journal": "Journal of psychoactive drugs", "publication_date": "2022-12-31", "publication_year": 2022, "doi": "10.1080/02791072.2021.2022254", "pubmed_id": "35000572", "source_url": "https://pubmed.ncbi.nlm.nih.gov/35000572/", "keywords": "3, 4-methyl enedioxy methamphetamine, LSD, Lysergic acid diethylamide, MDMA, ayahuasca, bibliometric analysis, drug-psychotherapy combination, psilocybin, psychedelics, research evaluation, scientometrics", "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\":\"35000572\"}", "topic_tags": "Chronic Pain,Healthcare Workers", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1505, "title": "Psychedelic-induced mystical experiences: An interdisciplinary discussion and critique.", "normalized_title": "psychedelic induced mystical experiences an interdisciplinary discussion and critique", "authors": "Mosurinjohn S, Roseman L, Girn M", "abstract": "Contemporary research on serotonergic psychedelic compounds has been rife with references to so-called 'mystical' subjective effects. Several psychometric assessments have been used to assess such effects, and clinical studies have found quantitative associations between 'mystical experiences' and positive mental health outcomes. The nascent study of psychedelic-induced mystical experiences, however, has only minimally intersected with relevant contemporary scholarship from disciplines within the social sciences and humanities, such as religious studies and anthropology. Viewed from the perspective of these disciplines-which feature rich historical and cultural literatures on mysticism, religion, and related topics-'mysticism' as used in psychedelic research is fraught with limitations and intrinsic biases that are seldom acknowledged. Most notably, existing operationalizations of mystical experiences in psychedelic science fail to historicize the concept and therefore fail to acknowledge its perennialist and specifically Christian bias. Here, we trace the historical genesis of the mystical in psychedelic research in order to illuminate such biases, and also offer suggestions toward more nuanced and culturally-sensitive operationalizations of this phenomenon. In addition, we argue for the value of, and outline, complementary 'non-mystical' approaches to understanding putative mystical-type phenomena that may help facilitate empirical investigation and create linkages to existing neuro-psychological constructs. It is our hope that the present paper helps build interdisciplinary bridges that motivate fruitful paths toward stronger theoretical and empirical approaches in the study of psychedelic-induced mystical experiences.", "journal": "Frontiers in psychiatry", "publication_date": "2022-12-31", "publication_year": 2022, "doi": "10.3389/fpsyt.2023.1077311", "pubmed_id": "37181886", "source_url": "https://pubmed.ncbi.nlm.nih.gov/37181886/", "keywords": "mystical experience, mystical experience questionnaire, psilocybin, psychedelics, religious studies", "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\":\"37181886\"}", "topic_tags": "Mystical Experience", "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": 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": 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": 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": 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": 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": 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": 1732, "title": "Editorial: Psychedelic sociality: Pharmacological and extrapharmacological perspectives.", "normalized_title": "editorial psychedelic sociality pharmacological and extrapharmacological perspectives", "authors": "Roseman L, Preller KH, Fotiou E, Winkelman MJ", "abstract": "", "journal": "Frontiers in pharmacology", "publication_date": "2021-12-31", "publication_year": 2021, "doi": "10.3389/fphar.2022.979764", "pubmed_id": "35935854", "source_url": "https://pubmed.ncbi.nlm.nih.gov/35935854/", "keywords": "5-HT2A receptor, LSD, biopsychosocial, culture, interdisciplinary research, psilocybin, set and setting, social pharmacology", "substance_tags": "psilocybin", "source_name": "PubMed", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:20:39", "raw_json": "{\"pubmed_id\":\"35935854\"}", "topic_tags": "Pharmacology,Receptor Pharmacology", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" } ] }