{ "meta": { "tracker_site_url": "https://psilocybin-research.com", "publication_tracker_url": "https://psilocybin-research.com/", "generated_at_utc": "2026-07-02 19:55:22", "record_count": 39 }, "papers": [ { "id": 3023, "title": "Distinct brain responses to psilocybin and escitalopram in depression captured by the Fluctuation-Dissipation Theorem", "normalized_title": "distinct brain responses to psilocybin and escitalopram in depression captured by the fluctuation dissipation theorem", "authors": "Dagnino PC, Acero-Pousa I, Zamora-López G, Escrichs A, Erritzoe D, Nutt DJ, Carhart-Harris RL, Sanz Perl Y, Kringelbach ML, Deco G.", "abstract": "In recent decades, the psychedelic psilocybin has been studied as a potential treatment for major depressive disorder (MDD), offering an alternative to traditional antidepressants. However, the brain changes underlying the clinical effects of different interventions remain unclear. Here, we investigated the effects of psilocybin and a conventional antidepressant, escitalopram, from the double-blind randomised controlled trial (DB-RCT) - NCT03429075 - on the brain’s hierarchical organisation. Using pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) we built whole-brain models and obtained a generative effective connectivity (GEC) matrix for each patient. Based on the GEC, we measured the level of non-equilibrium brain dynamics by quantifying the deviation from the fluctuation-dissipation theorem (FDT) and performed complementary analysis on brain segregation and asymmetry. Our results showed opposite reconfigurations of the hierarchical non-equilibrium brain dynamics following each treatment. Additionally, baseline measures effectively distinguished responders from non-responders within each treatment. These findings suggest that the deviation of the FDT may serve as a marker for differentiating the effects of psilocybin and escitalopram in MDD treatment, overall, contributing to the understanding of therapeutic mechanisms of depression.", "journal": "bioRxiv", "publication_date": "2026-06-15", "publication_year": 2026, "doi": "10.64898/2026.06.12.731811", "pubmed_id": null, "source_url": "https://doi.org/10.64898/2026.06.12.731811", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:45", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"PPR1253375\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Randomized Controlled Trial", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3711, "title": "The entropic brain today.", "normalized_title": "the entropic brain today", "authors": "Carhart-Harris RL.", "abstract": "Introduced in 2014 and revised in 2018, the entropic brain hypothesis has accrued a wealth of supportive evidence. The hypothesis states that-along a dimension of the size of phenomenal consciousness-expansive states reliably exhibit increased brain entropy whereas the inverse applies for states of no or reduced consciousness. Examples of expansive states include expert meditation, flicker light stimulation, near-death-like experiences, atypical breathing, rapid-eye-movement sleep, the pre-ictal aura, unmedicated early psychosis and psychedelic drug states. Examples of states of no or reduced consciousness with low brain entropy, include disorders of consciousness, deep sleep, the anesthetized state, seizure, post-stroke, ageing, cognitive impairment, and neurodegenerative illness. It is shown that the entropic brain has convergent, correlative, predictive, discriminative and external validity. Regarding its predictive validity, increased brain entropy under psilocybin (in a supportive context) predicts subsequent improvements in mental health (improved wellbeing 1-month post-dose). Regarding its discriminative validity, changes in brain entropy selectively index the breadth of subjective experience versus alternative dimensions, such as arousal. Regarding portability/external validity, an entropy-related function is applied in generative artificial intelligence. In conclusion, the entropic brain is a useful model of conscious states.", "journal": null, "publication_date": "2026-06-09", "publication_year": 2026, "doi": "10.1093/brain/awag206", "pubmed_id": "42266156", "source_url": "https://doi.org/10.1093/brain/awag206", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:08:38", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"42266156\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Aging,Wellbeing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 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": 457, "title": "N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences.", "normalized_title": "n n dimethyltryptamine effects on connectome harmonics subjective experience and comparative psychedelic experiences", "authors": "Vohryzek J, Luppi AI, Atasoy S, Deco G, Carhart-Harris RL, Timmermann C, Kringelbach ML.", "abstract": "Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome - a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under N,N-dimethyltryptamine (DMT) is reshaped in line with other reported psychedelic compounds - psilocybin, lysergic acid diethylamide (LSD) and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics index the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.", "journal": null, "publication_date": "2025-09-11", "publication_year": 2025, "doi": "10.1038/s41386-025-02190-4", "pubmed_id": "40940591", "source_url": "https://doi.org/10.1038/s41386-025-02190-4", "keywords": "Brain, Nerve Net, Humans, N,N-Dimethyltryptamine, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Adult, Female, Male, Young Adult, Connectome, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"40940591\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Mechanism of Action,Consciousness,Aging", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3216, "title": "Accurate and Interpretable Prediction of Antidepressant Treatment Response from Receptor-informed Neuroimaging", "normalized_title": "accurate and interpretable prediction of antidepressant treatment response from receptor informed neuroimaging", "authors": "Tolle HM, Luppi AI, Lawn T, Roseman L, Nutt D, Carhart-Harris RL, Mediano PAM.", "abstract": "Conventional antidepressants show moderate efficacy in treating major depressive disorder. Psychedelic-assisted therapy holds promise, yet individual responses vary, underscoring the need for predictive tools to guide treatment selection. Here, we present graphTRIP (graph-based Treatment Response Interpretability and Prediction) - a geometric deep learning architecture that enables three advances: 1) accurate prediction of post-treatment depression severity using only pretreatment clinical and neuroimaging data; 2) identification of robust biomarkers; and 3) causal analysis of treatment effects and underlying mechanisms. Trained on data from a clinical trial comparing psilocybin and escitalopram ( NCT03429075 ), graphTRIP achieves strong predictive accuracy ( r = 0.72, p = 6.8 ×10 −8 ), and shows clear generalization to both an independent dataset and across brain atlases. The model identifies stronger functional connectivity within sensory networks as a robust predictor of poorer response across both treatments. In contrast, causal analysis implicates frontoparietal and default mode networks as key moderators of differential response, with stronger 5-HT1A- and 5-HT2A-related signalling in the frontoparietal network predicting escitalopram response but psilocybin resistance. Overall, this work advances precision medicine and biomarker discovery in depression.", "journal": "bioRxiv", "publication_date": "2025-07-02", "publication_year": 2025, "doi": "10.1101/2025.07.02.662710", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2025.07.02.662710", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR1046304\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Biomarkers,Aging,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 635, "title": "Exploring serotonergic psychedelics as a treatment for personality disorders.", "normalized_title": "exploring serotonergic psychedelics as a treatment for personality disorders", "authors": "Carrithers BM, Roberts DE, Weiss BM, King JD, Carhart-Harris RL, Gordon AR, Pagni BA, Moreau M, Ross S, Zeifman RJ", "abstract": "Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy could hold potential for addressing core features of PDs through shared mechanisms of personality modulation. Although historical literature and observational studies suggest the potential clinical utility of psychedelics in treating PDs, rigorous research is lacking, and individuals with PDs are often excluded from modern psychedelic therapy trials. In the present review, we first discuss research on the effects of psychedelics in individuals with a PD through the conventional lens of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.; DSM-5-TR) categorical model. Next, using the dimensional DSM Alternative Model of Personality Disorders (DSM-AMPD) as a framework, we examine how psychedelics may affect self-functioning, interpersonal functioning, and pathological personality traits. We conclude by discussing the clinical relevance of psychedelic therapy as a treatment for personality pathology, including safety considerations, gaps and limitations, and recommendations for approaching psychedelic therapy within these more complex clinical populations.", "journal": "Neuropharmacology", "publication_date": "2025-06-30", "publication_year": 2025, "doi": "10.1016/j.neuropharm.2025.110413", "pubmed_id": "40081794", "source_url": "https://pubmed.ncbi.nlm.nih.gov/40081794/", "keywords": "Personality disorders, Personality traits, Psilocybin-assisted therapy, Psychedelics, Psychopharmacology, Psychotherapy", "substance_tags": "psilocybin", "source_name": "PubMed", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:20:35", "raw_json": "{\"pubmed_id\":\"40081794\"}", "topic_tags": "Pharmacology,Mechanism of Action,Personality Change,Review Article,Observational Study,Safety", "study_type": "Review Article", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 889, "title": "Human neuroimaging: fMRI.", "normalized_title": "human neuroimaging fmri", "authors": "Wall MB, Carhart-Harris RL.", "abstract": "Human neuroimaging with functional Magnetic Resonance Imaging has been a key feature of the current wave of psychedelic research, in both healthy and clinical populations. The available data has suggested that classic psychedelics (psilocybin, LSD, DMT) have a characteristic effect of acutely and profoundly disrupting the normal pattern of resting-state connectivity in the human brain, and that this effect may be closely related to both the characteristic subjective phenomenology of psychedelics, and their more clinically-relevant longer-term effects on emotional brain systems. This chapter briefly outlines the basic methodological background of fMRI, and then provides an overview of the current state of knowledge of psychedelic drug action as revealed by task and resting-state fMRI, in both non-clinical and clinical cohorts. Current limitations of the field are largely addressable by ongoing and future work, particularly in terms of providing additional datasets, increased standardisation of data acquisition and analysis procedures, potential multi-modal imaging studies, and more open data-sharing. Neuroimaging with fMRI remains a central platform of modern psychedelic research, with implications for our mechanistic understanding of psychedelics, as well as a strong influence on the clinical development of psychedelic-based treatments.", "journal": null, "publication_date": "2025-06-05", "publication_year": 2025, "doi": "10.1016/bs.irn.2025.04.013", "pubmed_id": "40541308", "source_url": "https://doi.org/10.1016/bs.irn.2025.04.013", "keywords": "Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Neuroimaging", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"40541308\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Aging,Emotional Processing,Observational Study", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 664, "title": "Enhanced meaning in life following psychedelic use: converging evidence from controlled and naturalistic studies.", "normalized_title": "enhanced meaning in life following psychedelic use converging evidence from controlled and naturalistic studies", "authors": "Roseby W, Kettner H, Roseman L, Spriggs MJ, Lyons T, Peill J, Giribaldi B, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "IntroductionPsychedelics, such as psilocybin, are increasingly recognized for their propensity to elicit powerful subjective experiences that carry personal meaning. While research has demonstrated the capacity for these compounds to promote psychological wellbeing, it has yet to be shown to what extent they modulate \"meaning in life\", a specific contributor to mental and physical health.MethodsUsing the Meaning in Life Questionnaire (MLQ), we examined changes in meaning in life occurring across three different contexts of psychedelic use, including a randomized clinical trial of psilocybin for depression, controlled administration of psilocybin in a single-arm healthy volunteer study, and a naturalistic observational study following participants in psychedelic retreats. Meaning in life changes were analyzed with linear mixed models, and relationships to other predictors and outcomes were examined via Pearson correlations.ResultsAcross all contexts, the sub-factor \"presence of meaning\" was strongly increased after a psychedelic experience, while the sub-factor \"search for meaning\" was only weakly reduced. Enhancements of meaning in life were also moderately correlated with changes in measures of mental health, including mental wellbeing and depression severity. In line with previous research, we found that mystical, ego dissolution and emotional breakthrough experiences were correlated with an increase of meaning in life, with context-dependent differences in the strength of the association.DiscussionThe convergence of evidence from multiple studies shows that psychedelic use has a robust and long-lasting positive effect on meaning in life. We explore potential mechanisms of psychedelic-induced meaning enhancement and highlight the possible influences of psychosocial context on outcomes.", "journal": null, "publication_date": "2025-06-05", "publication_year": 2025, "doi": "10.3389/fpsyg.2025.1580663", "pubmed_id": "40547590", "source_url": "https://doi.org/10.3389/fpsyg.2025.1580663", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"40547590\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Wellbeing,Emotional Processing,Mystical Experience,Clinical Trial,Observational Study,Healthy Volunteers", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 675, "title": "Reduced Brain Responsiveness to Emotional Stimuli With Escitalopram But Not Psilocybin Therapy for Depression.", "normalized_title": "reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression", "authors": "Wall MB, Demetriou L, Giribaldi B, Roseman L, Ertl N, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "ObjectivePsilocybin is an emerging intervention for depression that may be at least as effective as selective serotonin reuptake inhibitors (SSRIs), but effects of the two treatments on the neural correlates of emotional processing have never been directly compared.MethodsThe authors assessed neural responses to emotional faces using blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) in two groups with major depression. One group (N=25; 9 women and 16 men) received two dosing sessions with 25 mg psilocybin plus 6 weeks of daily inert placebo, and the second group (N=21; 6 women and 15 men) received 6 weeks of escitalopram plus two dosing sessions with a nonpsychoactive (placebo) dose of 1 mg psilocybin. Both groups had equal psychological support throughout: 3 hours of preparation, one in-person integration session following the psilocybin dosing sessions, and two further integration sessions conducted via video call or telephone. An emotional face fMRI paradigm was completed before treatment and at the 6-week posttreatment primary end point (3 weeks following psilocybin dosing sessions).ResultsPatient group (psilocybin versus escitalopram) interacted with time point (before versus after treatment) on a distributed set of cortical regions. Post hoc within-condition analyses showed that posttreatment BOLD responses to emotional faces of all types were significantly reduced in the escitalopram group, with no change or a slight increase in the psilocybin group. Analyses of amygdala responsivity showed a reduction of response to fearful faces in the escitalopram group, but lesser effects for the psilocybin group.ConclusionsDespite large improvements in depressive symptoms in the psilocybin group, psilocybin therapy had only a minor effect on brain responsiveness to emotional stimuli. These results are consistent with prior findings that the antidepressant action of SSRIs is often accompanied by a reduction in emotional responsiveness, but this effect may not occur in psychedelic therapy.", "journal": null, "publication_date": "2025-05-06", "publication_year": 2025, "doi": "10.1176/appi.ajp.20230751", "pubmed_id": "40329640", "source_url": "https://doi.org/10.1176/appi.ajp.20230751", "keywords": "Brain, Amygdala, Humans, Hallucinogens, Magnetic Resonance Imaging, Facial Expression, Treatment Outcome, Double-Blind Method, Emotions, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"40329640\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Receptor Pharmacology,Aging,Emotional Processing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 824, "title": "A qualitative analysis of the psychedelic mushroom come-up and come-down.", "normalized_title": "a qualitative analysis of the psychedelic mushroom come up and come down", "authors": "Brouwer A, Brown JK, Erowid E, Erowid F, Thyssen S, Raison CL, Carhart-Harris RL.", "abstract": "Psychedelic therapy has the potential to become a revolutionary and transdiagnostic mental health treatment, yielding enduring benefits that are often attributed to the experiences that coincide with peak psychedelic effects. However, there may be an underrecognized temporal structure to this process that helps explain why psychedelic and related altered states of consciousness can have an initially distressing but ultimately distress-resolving effect. Here we present a qualitative analysis of the self-reported 'come-up' or onset phase, and 'come-down' or falling phase, of the psychedelic experience. Focusing on psilocybin or psilocybin-containing mushroom experience reports submitted to Erowid.org, we use phenomenological, thematic content and word frequency analysis to show that the come-up is more often characterized by negatively valenced feeling states that resemble an acute stress reaction, while the come-down phase is more often characterized by positively valenced feeling states of the sort often observed following recovery from illness or resolution of stress. The therapeutic and theoretical relevance of these findings are discussed.", "journal": null, "publication_date": "2025-02-06", "publication_year": 2025, "doi": "10.1038/s44184-024-00095-6", "pubmed_id": "39915687", "source_url": "https://doi.org/10.1038/s44184-024-00095-6", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"39915687\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 850, "title": "From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS).", "normalized_title": "from relaxed beliefs under psychedelics rebus to revised beliefs after psychedelics rebas", "authors": "Zeifman RJ, Spriggs MJ, Kettner H, Lyons T, Rosas FE, Mediano PAM, Erritzoe D, Carhart-Harris RL.", "abstract": "The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; which (b) facilitate positive therapeutic outcomes and are associated with the entropy of EEG signals. Healthy individuals (N = 11) were administered 1 mg and 25 mg psilocybin 4-weeks apart. Confidence ratings for personally held beliefs were obtained before, during, and 4-weeks post-psilocybin. Acute entropy and subjective experiences were measured, as was well-being (before and 4-weeks post-psilocybin). Confidence in negative self-beliefs decreased following 25 mg psilocybin. Entropy and subjective effects under 25 mg psilocybin correlated with decreases in negative self-belief confidence (acutely and at 4-weeks). Particularly strong evidence was seen for a relationship between decreases in negative self-belief confidence and increases in well-being. We report the first empirical evidence that the relaxation and revision of negative self-belief confidence mediates psilocybin's positive psychological outcomes, and provide tentative evidence for a neuronal mechanism, namely, increased neuronal entropy. Replication within larger and clinical samples is necessary. We also introduce a new measure for examining the robustness of these preliminary findings and the utility of the REBUS model.", "journal": null, "publication_date": "2025-01-28", "publication_year": 2025, "doi": "10.1038/s41598-023-28111-3", "pubmed_id": "39881126", "source_url": "https://doi.org/10.1038/s41598-023-28111-3", "keywords": "Humans, Hallucinogens, Electroencephalography, Adult, Female, Male, Young Adult, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"39881126\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Wellbeing", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 1128, "title": "Time-resolved coupling between connectome harmonics and subjective experience under the psychedelic DMT", "normalized_title": "time resolved coupling between connectome harmonics and subjective experience under the psychedelic dmt", "authors": "Vohryzek J, Luppi A, Atasoy S, Deco G, Timmermann C, Carhart-Harris RL, Kringelbach ML.", "abstract": "Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome, a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under DMT is reshaped in line with other reported psychedelic compounds; psilocybin, LSD and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics indexes the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.", "journal": "bioRxiv", "publication_date": "2024-05-30", "publication_year": 2024, "doi": "10.1101/2024.05.30.596410", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2024.05.30.596410", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"PPR860621\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Mechanism of Action,Consciousness", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3282, "title": "The Temporal Trajectory of the Psychedelic Mushroom Experience Mimics the Narrative Arc of the Hero’s Journey", "normalized_title": "the temporal trajectory of the psychedelic mushroom experience mimics the narrative arc of the hero s journey", "authors": "Brouwer A, Brown JK, Erowid E, Erowid F, Thyssen S, Raison CL, Carhart-Harris RL.", "abstract": "Abstract Psychedelic therapy has the potential to become a revolutionary and transdiagnostic mental health treatment, yielding enduring benefits that are often attributed to the experiences that coincide with peak psychedelic effects. However, there may be an underrecognized temporal structure to this process that helps explain why psychedelic and related altered states of consciousness can have a initially distressing but ultimately a distress-resolving effect. Here we present a qualitative analysis of the self-reported ‘comeup’ or onset phase, and ‘comedown’ or falling phase, of the psychedelic experience. Focusing on psilocybin or psilocybin-containing mushrooms, we show that the comeup is more often characterized by negatively valenced feeling states, while the comedown phase is more often characterized by positively valenced feeling states of the sort often observed following recovery from illness or adversity. In this way, the temporal trajectory of the psychedelic experience could be seen to mimic the narrative arc of the monomythical ‘Hero’s Journey’.", "journal": "Research Square", "publication_date": "2024-02-22", "publication_year": 2024, "doi": "10.21203/rs.3.rs-3941205/v1", "pubmed_id": null, "source_url": "https://doi.org/10.21203/rs.3.rs-3941205/v1", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:03:49", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"PPR810141\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"Research Square\",\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1224, "title": "Brain dynamics predictive of response to psilocybin for treatment-resistant depression.", "normalized_title": "brain dynamics predictive of response to psilocybin for treatment resistant depression", "authors": "Vohryzek J, Cabral J, Lord LD, Fernandes HM, Roseman L, Nutt DJ, Carhart-Harris RL, Deco G, Kringelbach ML.", "abstract": "Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here, we leveraged the differential outcome in responders and non-responders to psilocybin (10 and 25 mg, 7 days apart) therapy for depression-to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a healthy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-hydroxytryptamine 2a and 5-hydroxytryptamine 1a, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression, and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.", "journal": null, "publication_date": "2024-02-14", "publication_year": 2024, "doi": "10.1093/braincomms/fcae049", "pubmed_id": "38515439", "source_url": "https://doi.org/10.1093/braincomms/fcae049", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"38515439\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1233, "title": "Effects of DMT on mental health outcomes in healthy volunteers.", "normalized_title": "effects of dmt on mental health outcomes in healthy volunteers", "authors": "Timmermann C, Zeifman RJ, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin's acute effects (4-6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via 'Oceanic Boundlessness'). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.", "journal": null, "publication_date": "2024-02-06", "publication_year": 2024, "doi": "10.1038/s41598-024-53363-y", "pubmed_id": "38326357", "source_url": "https://doi.org/10.1038/s41598-024-53363-y", "keywords": "Humans, N,N-Dimethyltryptamine, Hallucinogens, Prospective Studies, Healthy Volunteers, Psilocybin, Outcome Assessment, Health Care", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"38326357\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Wellbeing,Observational Study,Healthy Volunteers", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1286, "title": "Psilocybin and Other Classic Psychedelics in Depression.", "normalized_title": "psilocybin and other classic psychedelics in depression", "authors": "Nutt DJ, Peill JM, Weiss B, Godfrey K, Carhart-Harris RL, Erritzoe D.", "abstract": "Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences, insightful and emotional breakthroughs as well as mystical-type experiences. When coupled with psychological support, effects can produce a rapid improvement in mood among people with depression that can last for months. In this chapter, we summarise the scientific studies to date that explore the use of psychedelics in depressed individuals, highlighting key clinical, psychological and neuroimaging features of psychedelics that may account for their therapeutic effects. These include alterations in brain entropy that disrupt fixed negative ruminations, a period of post-treatment increased cognitive flexibility, and changes in self-referential psychological processes. Finally, we propose that the brain mechanisms underlying the therapeutic effect of serotonergic psychedelics might be distinct from those underlying classical serotonin reuptake-blocking antidepressants.", "journal": null, "publication_date": "2023-12-31", "publication_year": 2023, "doi": "10.1007/7854_2023_451", "pubmed_id": "37955822", "source_url": "https://doi.org/10.1007/7854_2023_451", "keywords": "Brain, Humans, Hallucinogens, Depression, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"37955822\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Emotional Processing,Mystical Experience", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3342, "title": "Statistical diversity distinguishes global states of consciousness", "normalized_title": "statistical diversity distinguishes global states of consciousness", "authors": "Starkey J, Carhart-Harris RL, Pigorini A, Nobili L, Barrett AB.", "abstract": "Application of complexity measures to neurophysiological time series has seen increased use in recent years to identify neural correlates of global states of consciousness. Lempel-Ziv complexity is currently the de-facto complexity measure used in these investigations. However, by simply counting the number of patterns, this measure theoretically takes its maximum value for data that are completely random. Recently, a measure of ‘statistical complexity’ - which calculates the diversity of statistical interactions - has been devised which aims to account for and remove randomness seen in data. It was recently found that this measure decreases during anaesthesia in fruit flies. This paper investigates this statistical complexity measure on human neurophysiology data from different stages of sleep, and from individuals under the effects of three psychedelic substances: ketamine, lysergic acid diethylamide (LSD), and psilocybin. Results indicate that statistical complexity: (i) differentiates the different stages of sleep analogously to Lempel-Ziv complexity; (ii) increases relative to placebo for all three psychedelic substances. Thus, statistical complexity is a useful alternative measure for investigating the complexity of neural activity associated with different states of consciousness.", "journal": "bioRxiv", "publication_date": "2023-12-06", "publication_year": 2023, "doi": "10.1101/2023.12.05.570101", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2023.12.05.570101", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:51", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"PPR770814\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Consciousness,Drug Interactions", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3351, "title": "The entropic heart: Tracking the psychedelic state via heart rate dynamics", "normalized_title": "the entropic heart tracking the psychedelic state via heart rate dynamics", "authors": "Rosas FE, Mediano PA, Timmermann C, Luppi AI, Candia-Rivera D, Abbasi-Asl R, Gazzaley A, Kringelbach ML, Muthukumaraswamy S, Bor D, Garfinkel S, Carhart-Harris RL.", "abstract": "A growing body of work shows that autonomic signals provide a privileged evidence-stream to capture various aspects of subjective and neural states. This work investigates the potential for autonomic markers to track the effects of psychedelics - potent psychoactive drugs with important scientific and clinical value. For this purpose, we introduce a novel Bayesian framework to estimate the entropy of heart rate dynamics under psychedelics. We also calculate Bayesian estimates of mean heart rate and heart rate variability, and investigate how these measures relate to subjective reports and neural effects. Results on datasets covering four drugs - lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), psilocybin, and sub-anaesthetic doses of the dissociative agent ketamine - show consistent increases in mean heart rate, high-frequency heart rate variability, and heart rate entropy during the psychedelic experience. Moreover, these effects have predictive power over various dimensions of the psychedelic experience. Changes in heart rate entropy were found to be correlated with increases in brain entropy, while other autonomic markers were not. Overall, our results show that a cost-efficient autonomic measure has the potential to reveal surprising detail about subjective and brain states, opening up a range of new research avenues to explore in both basic and clinical neuroscience.", "journal": "bioRxiv", "publication_date": "2023-11-08", "publication_year": 2023, "doi": "10.1101/2023.11.07.566008", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2023.11.07.566008", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:51", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"PPR756922\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Biomarkers", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1407, "title": "Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences.", "normalized_title": "co use of mdma with psilocybin lsd may buffer against challenging experiences and enhance positive experiences", "authors": "Zeifman RJ, Kettner H, Pagni BA, Mallard A, Roberts DE, Erritzoe D, Ross S, Carhart-Harris RL.", "abstract": "Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium-high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose-response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted and may assist the development of personalized treatments.", "journal": null, "publication_date": "2023-08-21", "publication_year": 2023, "doi": "10.1038/s41598-023-40856-5", "pubmed_id": "37608057", "source_url": "https://doi.org/10.1038/s41598-023-40856-5", "keywords": "Humans, Methamphetamine, Hallucinogens, Prospective Studies, Fear, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"37608057\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Mystical Experience,Safety", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1293, "title": "Personality Change in a Trial of Psilocybin Therapy vs Escitalopram Treatment for Depression - CORRIGENDUM.", "normalized_title": "personality change in a trial of psilocybin therapy vs escitalopram treatment for depression corrigendum", "authors": "Weiss B, Ginige I, Shannon L, Giribaldi B, Murphy-Beiner A, Murphy R, Baker-Jones M, Martell J, Nutt DJ, Carhart-Harris RL, Erritzoe D.", "abstract": "", "journal": null, "publication_date": "2023-07-18", "publication_year": 2023, "doi": "10.1017/s0033291723002039", "pubmed_id": "37466289", "source_url": "https://doi.org/10.1017/s0033291723002039", "keywords": "Humans, Citalopram, Hallucinogens, Depression, Personality, Personality Disorders, Psilocybin, Escitalopram", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"37466289\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Personality Change", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1464, "title": "In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape.", "normalized_title": "in vivo mapping of pharmacologically induced functional reorganization onto the human brain s neurotransmitter landscape", "authors": "Luppi AI, Hansen JY, Adapa R, Carhart-Harris RL, Roseman L, Timmermann C, Golkowski D, Ranft A, Ilg R, Jordan D, Bonhomme V, Vanhaudenhuyse A, Demertzi A, Jaquet O, Bahri MA, Alnagger NLN, Cardone P, Peattie ARD, Manktelow AE, de Araujo DB, Sensi SL, Owen AM, Naci L, Menon DK, Misic B, Stamatakis EA.", "abstract": "To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain's rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradients of brain structure and function. Last, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganization of the brain's functional architecture.", "journal": null, "publication_date": "2023-06-13", "publication_year": 2023, "doi": "10.1126/sciadv.adf8332", "pubmed_id": "37315149", "source_url": "https://doi.org/10.1126/sciadv.adf8332", "keywords": "Brain, Humans, Methylphenidate, Ketamine, Membrane Transport Proteins, Modafinil", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"37315149\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Receptor Pharmacology,Aging", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3153, "title": "Reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression", "normalized_title": "reduced brain responsiveness to emotional stimuli with escitalopram but not psilocybin therapy for depression", "authors": "Wall MB, Demetriou L, Giribaldi B, Roseman L, Ertl N, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "Psilocybin therapy is an emerging intervention for depression that may be at least as effective as standard first-line treatments i.e., Selective Serotonin Reuptake Inhibitors (SSRIs). Here we assess neural responses to emotional faces (fear, happy, and neutral) using Blood Oxygen-Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) in two groups with major depressive disorder: 1) a ‘psilocybin group’ that received two dosing sessions with 25mg plus six weeks of daily placebo, and 2) an ‘escitalopram group’ that received six weeks of the SSRI escitalopram, plus two dosing sessions with an inactive/placebo dose of 1mg psilocybin. Both groups had an equal amount of psychological support throughout. An emotional face fMRI paradigm was completed at baseline (pre-treatment) and at the six-week post-treatment primary endpoint (three weeks following psilocybin dosing sessions). An analysis examining the interaction between patient group (psilocybin vs. escitalopram) and time-point (pre-vs. post-treatment) showed a robust effect in a distributed network of cortical brain regions. Follow-up analyses showed that post-treatment BOLD responses to emotional faces of all types were significantly reduced in the escitalopram group, with no change, or even a slight increase, in the psilocybin group. Specific analyses of the amygdala showed a reduction of response to fear faces in the escitalopram group, but no effects for the psilocybin group. Despite large improvements in depressive symptoms in the psilocybin group, psilocybin-therapy had only a minor effect on brain responsiveness to emotional stimuli. We suggest that reduced emotional responsiveness may be a biomarker of SSRIs’ antidepressant action that is not shared by psilocybin-therapy.", "journal": "medRxiv", "publication_date": "2023-06-02", "publication_year": 2023, "doi": "10.1101/2023.05.29.23290667", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2023.05.29.23290667", "keywords": "", "substance_tags": "psilocybin", "source_name": "medRxiv", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR670172\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"medRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Receptor Pharmacology,Biomarkers,Aging,Emotional Processing,Drug Interactions", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1295, "title": "Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression.", "normalized_title": "personality change in a trial of psilocybin therapy v escitalopram treatment for depression", "authors": "Weiss B, Ginige I, Shannon L, Giribaldi B, Murphy-Beiner A, Murphy R, Baker-Jones M, Martell J, Nutt DJ, Carhart-Harris RL, Erritzoe D.", "abstract": "BackgroundPsilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.MethodsIn a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.ResultsPT was associated with decreases in neuroticism (B = -0.63), introversion (B = -0.38), disagreeableness (B = -0.47), impulsivity (B = -0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = -0.47) and disagreeableness (B = -0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = -0.38), disagreeableness (B = -0.26), impulsivity (B = -0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = -0.46) remaining decreased at month 6. No significant between-condition differences were observed.ConclusionsPersonality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.", "journal": null, "publication_date": "2023-06-01", "publication_year": 2023, "doi": "10.1017/s0033291723001514", "pubmed_id": "37264814", "source_url": "https://doi.org/10.1017/s0033291723001514", "keywords": "Humans, Depression, Personality, Psilocybin, Neuroticism, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"37264814\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Personality Change,Clinical Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1487, "title": "Time-resolved network control analysis links reduced control energy under DMT with the serotonin 2a receptor, signal diversity, and subjective experience", "normalized_title": "time resolved network control analysis links reduced control energy under dmt with the serotonin 2a receptor signal diversity and subjective experience", "authors": "Singleton SP, Timmermann C, Luppi AI, Eckernäs E, Roseman L, Carhart-Harris RL, Kuceyeski A.", "abstract": "Psychedelics offer a profound window into the functioning of the human brain and mind through their robust acute effects on perception, subjective experience, and brain activity patterns. In recent work using a receptor-informed network control theory framework, we demonstrated that the serotonergic psychedelics lysergic acid diethylamide (LSD) and psilocybin flatten the brain’s control energy landscape in a manner that covaries with more dynamic and entropic brain activity. Contrary to LSD and psilocybin, whose effects last for hours, the serotonergic psychedelic N,N-dimethyltryptamine (DMT) rapidly induces a profoundly immersive altered state of consciousness lasting less than 20 minutes, allowing for the entirety of the drug experience to be captured during a single resting-state fMRI scan. Using network control theory, which quantifies the amount of input necessary to drive transitions between functional brain states, we integrate brain structure and function to map the energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Consistent with previous work, we find that global control energy is reduced following injection with DMT compared to placebo. We additionally show longitudinal trajectories of global control energy correlate with longitudinal trajectories of EEG signal diversity (a measure of entropy) and subjective ratings of drug intensity. We interrogate these same relationships on a regional level and find that the spatial patterns of DMT’s effects on these metrics are correlated with serotonin 2a receptor density (obtained from separately acquired PET data). Using receptor distribution and pharmacokinetic information, we were able to successfully recapitulate the effects of DMT on global control energy trajectories, demonstrating a proof-of-concept for the use of control models in predicting pharmacological intervention effects on brain dynamics.", "journal": "bioRxiv", "publication_date": "2023-05-11", "publication_year": 2023, "doi": "10.1101/2023.05.11.540409", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2023.05.11.540409", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"PPR659698\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Brain Imaging,Pharmacology,Receptor Pharmacology,Consciousness", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1422, "title": "How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change.", "normalized_title": "how does psilocybin therapy work an exploration of experiential avoidance as a putative mechanism of change", "authors": "Zeifman RJ, Wagner AC, Monson CM, Carhart-Harris RL.", "abstract": "BackgroundPsilocybin therapy is receiving attention as a mental health intervention with transdiagnostic potential. In line with psychotherapeutic research, qualitative research has highlighted the role of reductions in experiential avoidance (and increases in connectedness) within psilocybin therapy. However, no quantitative research has examined experiential avoidance as a mechanism underlying psilocybin therapy's therapeutic effects.MethodData was used from a double-blind randomized controlled trial that compared psilocybin therapy (two 25 mg psilocybin session plus daily placebo for six weeks) with escitalopram (two 1 mg psilocybin sessions plus 10-20 mg daily escitalopram for six weeks) among individuals with major depressive disorder (N = 59). All participants received psychological support. Experiential avoidance, connectedness, and treatment outcomes were measured at pre-treatment and at a 6 week primary endpoint. Acute psilocybin experiences and psychological insight were also measured.ResultsWith psilocybin therapy, but not escitalopram, improvements in mental health outcomes (i.e., well-being, depression severity, suicidal ideation, and trait anxiety) occurred via reductions in experiential avoidance. Exploratory analyses suggested that improvements in mental health (except for suicidal ideation) via reduction in experiential avoidance were serially mediated through increases in connectedness. Additionally, experiences of ego dissolution and psychological insight predicted reductions in experiential avoidance following psilocybin therapy.LimitationsDifficulties inferring temporal causality, maintaining blindness to condition, and reliance upon self-report.ConclusionsThese results provide support for the role of reduced experiential avoidance as a putative mechanism underlying psilocybin therapy's positive therapeutic outcomes. The present findings may help to tailor, refine, and optimize psilocybin therapy and its delivery.", "journal": null, "publication_date": "2023-05-02", "publication_year": 2023, "doi": "10.1016/j.jad.2023.04.105", "pubmed_id": "37146908", "source_url": "https://doi.org/10.1016/j.jad.2023.04.105", "keywords": "Humans, Treatment Outcome, Anxiety, Anxiety Disorders, Psilocybin, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"37146908\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Wellbeing,Randomized Controlled Trial", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1449, "title": "A critical evaluation of QIDS-SR-16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression.", "normalized_title": "a critical evaluation of qids sr 16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression", "authors": "Weiss B, Erritzoe D, Giribaldi B, Nutt DJ, Carhart-Harris RL.", "abstract": "BackgroundIn a recent clinical trial examining the comparative efficacy of psilocybin therapy (PT) versus escitalopram treatment (ET) for major depressive disorder, 14 of 16 major efficacy outcome measures yielded results that favored PT, but the Quick Inventory of Depressive Symptomatology, Self-Report, 16 items (QIDS-SR16) did not.AimsThe present study aims to (1) rationally and psychometrically account for discrepant results between outcome measures and (2) to overcome psychometric problems particular to individual measures by re-examining between-condition differences in depressive response using all outcome measures at item-, facet-, and factor-levels of analysis.MethodFour depression measures were compared on the basis of their validity for examining differences in depressive response between PT and ET conditions.Results/outcomesPossible reasons for discrepant findings on the QIDS-SR16 include its higher variance, imprecision due to compound items and whole-scale and unidimensional sum-scoring, vagueness in the phrasing of scoring options for items, and its lack of focus on a core depression factor. Reanalyzing the trial data at item-, facet-, and factor-levels yielded results suggestive of PT's superior efficacy in reducing depressed mood, anhedonia, and a core depression factor, along with specific symptoms such as sexual dysfunction.Conclusion/interpretationOur results raise concerns about the adequacy of the QIDS-SR16 for measuring depression, as well as the practice of relying on individual scales that tend not to capture the multidimensional structure or core of depression. Using an alternative approach that captures depression more granularly and comprehensively yielded specific insight into areas where PT therapy may be particularly useful to patients and clinicians.", "journal": null, "publication_date": "2023-04-24", "publication_year": 2023, "doi": "10.1177/02698811231167848", "pubmed_id": "37122239", "source_url": "https://doi.org/10.1177/02698811231167848", "keywords": "Humans, Reproducibility of Results, Depression, Psychiatric Status Rating Scales, Clinical Trials as Topic, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:03", "raw_json": "{\"europe_pmc_id\":\"37122239\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Clinical Trial,Healthcare Workers", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1429, "title": "Increased low-frequency brain responses to music after psilocybin therapy for depression.", "normalized_title": "increased low frequency brain responses to music after psilocybin therapy for depression", "authors": "Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RL.", "abstract": "BackgroundPsychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following PT.MethodsBrain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of psilocybin dosing sessions.ResultsComparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions.LimitationsOpen-label trial. Relatively small sample size.ConclusionsThese data suggest an effect of PT on the brain's response to music, implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.", "journal": null, "publication_date": "2023-04-22", "publication_year": 2023, "doi": "10.1016/j.jad.2023.04.081", "pubmed_id": "37094657", "source_url": "https://doi.org/10.1016/j.jad.2023.04.081", "keywords": "Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Depression, Music, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"37094657\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Aging,Emotional Processing,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1594, "title": "Among psychedelic-experienced users, only past use of psilocybin reliably predicts nature relatedness.", "normalized_title": "among psychedelic experienced users only past use of psilocybin reliably predicts nature relatedness", "authors": "Forstmann M, Kettner HS, Sagioglou C, Irvine A, Gandy S, Carhart-Harris RL, Luke D.", "abstract": "BackgroundPast research reports a positive relationship between experience with classic serotonergic psychedelics and nature relatedness (NR). However, these studies typically do not distinguish between different psychedelic compounds, which have a unique psychopharmacology and may be used in specific contexts and with different intentions. Likewise, it is not clear whether these findings can be attributed to substance use per se or unrelated variables that differentiate psychedelic users from nonusers.AimsThe present study was designed to determine the relative degree to which lifetime experience with different psychedelic substances is predictive of self-reported NR among psychedelic-experienced users.MethodsWe conducted a combined reanalysis of five independent datasets (N = 3817). Using standard and regularized regression analyses, we tested the relationship between degree of experience with various psychedelic substances (binary and continuous) and NR, both within a subsample of psychedelic-experienced participants as well as the complete sample including psychedelic-naïve participants.Results/outcomesAmong people experienced with psychedelics, only past use of psilocybin (versus LSD, mescaline, Salvia divinorum, ketamine, and ibogaine) was a reliable predictor of NR and its subdimensions. Weaker, less reliable results were obtained for the pharmacologically similar N,N-dimethyltryptamine (DMT). Results replicate when including psychedelic-naïve participants. In addition, among people exclusively experience with psilocybin, use frequency positively predicted NR.Conclusions/interpretationResults suggest that experience with psilocybin is the only reliable (and strongest) predictor of NR. Future research should focus on psilocybin when investigating effects of psychedelic on NR and determine whether pharmacological attributes or differences in user expectations/use settings are responsible for this observation.", "journal": null, "publication_date": "2023-01-04", "publication_year": 2023, "doi": "10.1177/02698811221146356", "pubmed_id": "36601974", "source_url": "https://doi.org/10.1177/02698811221146356", "keywords": "Humans, N,N-Dimethyltryptamine, Mescaline, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"36601974\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Addiction,Pharmacology", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1528, "title": "Canalization and plasticity in psychopathology.", "normalized_title": "canalization and plasticity in psychopathology", "authors": "Carhart-Harris RL, Chandaria S, Erritzoe DE, Gazzaley A, Girn M, Kettner H, Mediano PAM, Nutt DJ, Rosas FE, Roseman L, Timmermann C, Weiss B, Zeifman RJ, Friston KJ.", "abstract": "This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, we call 'canalization', which is close to Hebbian plasticity. These two forms of plasticity can be most easily distinguished by their relationship to 'precision' or inverse variance; TEMP relates to increased model variance or decreased precision, whereas the opposite is true for canalization. TEMP also subsumes increased learning rate, (Ising) temperature and entropy. Dictionary definitions of 'plasticity' describe it as the property of being easily shaped or molded; TEMP is the better match for this. Importantly, we propose that 'pathological' phenotypes develop via mechanisms of canalization or increased model precision, as a defensive response to adversity and associated distress or dysphoria. Our model states that canalization entrenches in psychopathology, narrowing the phenotypic state-space as the agent develops expertise in their pathology. We suggest that TEMP - combined with gently guiding psychological support - can counter canalization. We address questions of whether and when canalization is adaptive versus maladaptive, furnish our model with references to basic and human neuroscience, and offer concrete experiments and measures to test its main hypotheses and implications. This article is part of the Special Issue on \"National Institutes of Health Psilocybin Research Speaker Series\".", "journal": null, "publication_date": "2022-12-26", "publication_year": 2022, "doi": "10.1016/j.neuropharm.2022.109398", "pubmed_id": "36584883", "source_url": "https://doi.org/10.1016/j.neuropharm.2022.109398", "keywords": "Humans, Learning, Phenotype, United States, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"36584883\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Neuroplasticity,Mechanism of Action", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 1719, "title": "Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample.", "normalized_title": "antidepressant effects of a psychedelic experience in a large prospective naturalistic sample", "authors": "Nygart VA, Pommerencke LM, Haijen E, Kettner H, Kaelen M, Mortensen EL, Nutt DJ, Carhart-Harris RL, Erritzoe D", "abstract": "Over the last two decades, a number of studies have highlighted the potential of psychedelic therapy. However, questions remain to what extend these results translate to naturalistic samples, and how contextual factors and the acute psychedelic experience relate to improvements in affective symptoms following psychedelic experiences outside labs/clinics. The present study sought to address this knowledge gap. Here, we aimed to investigate changes in anxiety and depression scores before versus after psychedelic experiences in naturalistic contexts, and how various pharmacological, extrapharmacological and experience factors related to outcomes. Individuals who planned to undergo a psychedelic experience were enrolled in this online survey study. Depressive symptoms were assessed at baseline and 2 and 4 weeks post-psychedelic experience, with self-rated Quick Inventory of Depressive Symptomatology (QIDS-SR-16) as the primary outcome. To facilitate clinical translation, only participants with depressive symptoms at baseline were included. Sample sizes for the four time points were = 302, = 182, = 155 and = 109, respectively. Relative to baseline, reductions in depressive symptoms were observed at 2 and 4 weeks. A medicinal motive, previous psychedelic use, drug dose and the type of acute psychedelic experience (i.e. specifically, having an emotional breakthrough) were all significantly associated with changes in self-rated QIDS-SR-16. These results lend support to therapeutic potential of psychedelics and highlight the influence of pharmacological and non-pharmacological factors in determining response. Mindful of a potential sample and attrition bias, further controlled and observational longitudinal studies are needed to test the replicability of these findings.", "journal": "Journal of psychopharmacology (Oxford, England)", "publication_date": "2022-07-31", "publication_year": 2022, "doi": "10.1177/02698811221101061", "pubmed_id": "35924888", "source_url": "https://pubmed.ncbi.nlm.nih.gov/35924888/", "keywords": "Psychedelics, anxiety, depression, mystical experience, psilocybin", "substance_tags": "psilocybin", "source_name": "PubMed", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:20:38", "raw_json": "{\"pubmed_id\":\"35924888\"}", "topic_tags": "Depression,Anxiety,Emotional Processing,Mystical Experience,Observational Study", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3372, "title": "Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape", "normalized_title": "mapping pharmacologically induced functional reorganisation onto the brain s neurotransmitter landscape", "authors": "Luppi AI, Hansen JY, Adapa R, Carhart-Harris RL, Roseman L, Timmermann C, Golkowski D, Golkowski D, Ranft A, Ilg R, Jordan D, Bonhomme V, Vanhaudenhuyse A, Demertzi A, Jaquet O, Bahri MA, Alnagger NL, Cardone P, Peattie ARD, Manktelow AE, de Araujo DB, Sensi SL, Owen AM, Naci L, Menon DK, Misic B, Stamatakis EA.", "abstract": "To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.", "journal": "bioRxiv", "publication_date": "2022-07-12", "publication_year": 2022, "doi": "10.1101/2022.07.12.499688", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2022.07.12.499688", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:51", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"PPR518432\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Receptor Pharmacology,Aging", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3131, "title": "Brain dynamics predictive of response to psilocybin for treatment-resistant depression", "normalized_title": "brain dynamics predictive of response to psilocybin for treatment resistant depression", "authors": "Vohryzek J, Cabral J, Lord L, Fernandes HM, Roseman L, Nutt DJ, Carhart-Harris RL, Deco G, Kringelbach ML.", "abstract": "Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT2A and 5-HT1A, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.", "journal": "bioRxiv", "publication_date": "2022-07-03", "publication_year": 2022, "doi": "10.1101/2022.06.30.497950", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2022.06.30.497950", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:47", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR521801\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 3731, "title": "Psychedelic resting-state neuroimaging: A review and perspective on balancing replication and novel analyses.", "normalized_title": "psychedelic resting state neuroimaging a review and perspective on balancing replication and novel analyses", "authors": "McCulloch DE, Knudsen GM, Barrett FS, Doss MK, Carhart-Harris RL, Rosas FE, Deco G, Kringelbach ML, Preller KH, Ramaekers JG, Mason NL, Müller F, Fisher PM", "abstract": "Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology. We offer guidelines for future studies that encourage coherence in the field. Psychedelic rs-fMRI will benefit from the development of novel methods that expand our understanding of the brain mechanisms mediating its intriguing effects; yet, this field is at a crossroads where we must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics.", "journal": "Neuroscience and biobehavioral reviews", "publication_date": "2022-06-30", "publication_year": 2022, "doi": "10.1016/j.neubiorev.2022.104689", "pubmed_id": "35588933", "source_url": "https://pubmed.ncbi.nlm.nih.gov/35588933/", "keywords": "Ayahausca, Clinical, DMT, Entheogen, FMRI, Hallucinogen, Human, LSD, Neuroimaging, Psilocin, Psilocybin, Psychedelic, Replication, Resting-state, Serotonin", "substance_tags": "psilocybin,psilocin", "source_name": "PubMed", "date_added": "2026-07-01 11:08:43", "last_checked": "2026-07-01 11:20:39", "raw_json": "{\"pubmed_id\":\"35588933\"}", "topic_tags": "Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Review Article", "study_type": "Review Article", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 3227, "title": "Increased low-frequency brain responses to music after psilocybin therapy for depression", "normalized_title": "increased low frequency brain responses to music after psilocybin therapy for depression", "authors": "Wall MB, Lam C, Ertl N, Kaelen M, Roseman L, Nutt DJ, Carhart-Harris RL.", "abstract": "Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain responses to music were assessed before and after PT using functional Magnetic Resonance Imaging (fMRI) and ALFF (Amplitude of Low Frequency Fluctuations) analysis methods. Nineteen patients with treatment-resistant depression underwent two treatment sessions involving administration of psilocybin, with MRI data acquired one week prior and the day after completion of the second of two psilocybin dosing sessions. Comparison of music-listening and resting-state scans revealed significantly greater ALFF in bilateral superior temporal cortex for the post-treatment music scan, and in the right ventral occipital lobe for the post-treatment resting-state scan. ROI analyses of these clusters revealed a significant effect of treatment in the superior temporal lobe for the music scan only. Somewhat consistently, voxelwise comparison of treatment effects showed relative increases for the music scan in the bilateral superior temporal lobes and supramarginal gyrus, and relative decreases in the medial frontal lobes for the resting-state scan. ALFF in these music-related clusters was significantly correlated with intensity of subjective effects felt during the dosing sessions. These data suggest a specific effect of PT on the brain’s response to a hedonic stimulus (music), implying an elevated responsiveness to music after psilocybin therapy that was related to subjective drug effects felt during dosing.", "journal": "bioRxiv", "publication_date": "2022-02-14", "publication_year": 2022, "doi": "10.1101/2022.02.13.480302", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2022.02.13.480302", "keywords": "", "substance_tags": "psilocybin", "source_name": "bioRxiv", "date_added": "2026-07-01 11:03:48", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"PPR454661\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"bioRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Brain Imaging,Aging,Emotional Processing,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 1894, "title": "Study Protocol for \"Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study\".", "normalized_title": "study protocol for psilocybin as a treatment for anorexia nervosa a pilot study", "authors": "Spriggs MJ, Douglass HM, Park RJ, Read T, Danby JL, de Magalhães FJC, Alderton KL, Williams TM, Blemings A, Lafrance A, Nicholls DE, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present (1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and (2) a protocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin. Methods: (1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of \"recovery\" from the perspective of those with lived experience. (2) Protocol: Twenty female participants [21-65 years old, body mass index (BMI) 15 kg/m2 or above] will receive three oral doses of psilocybin (up to 25 mg) over a 6-week period delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our two-fold primary outcomes are (1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and (2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: (1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and (2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity. Discussion: The results of this pilot study will not only shed light on the acceptability, brain mechanisms, and impression of the potential efficacy of psilocybin as an adjunct treatment for AN but will be essential in shaping a subsequent Randomised Control Trial (RCT) that would test this treatment against a suitable control condition. Clinical Trial Registration: identifier: NCT04505189.", "journal": null, "publication_date": "2021-10-19", "publication_year": 2021, "doi": "10.3389/fpsyt.2021.735523", "pubmed_id": "34744825", "source_url": "https://doi.org/10.3389/fpsyt.2021.735523", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:06", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"34744825\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Eating Disorders,End-of-Life Distress,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Clinical Trial,Randomized Controlled Trial", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" } ] }