{ "meta": { "tracker_site_url": "https://psilocybin-research.com", "publication_tracker_url": "https://psilocybin-research.com/", "generated_at_utc": "2026-07-02 18:47:04", "record_count": 38 }, "papers": [ { "id": 19, "title": "The Australia story: Current status and future challenges for the clinical applications of psychedelics.", "normalized_title": "the australia story current status and future challenges for the clinical applications of psychedelics", "authors": "Nutt DJ, Hunt P, Schlag AK, Fitzgerald P", "abstract": "The past decade has seen a huge increase in clinical research with psychedelic drugs and 3,4-methylenedioxymethamphetamine (MDMA), which have revealed great potential for treating mental health conditions. Given this progress in research, as well as the current unmet clinical need of millions of patients, in 2023, the Australian Therapeutic Goods Administration (TGA) approved the use of psilocybin for treatment-resistant depression and MDMA for PTSD to take effect from 1 July 2023. The campaign for TGA approval was led by a coalition comprising the Australian charity Mind Medicine Australia with support from Professor David Nutt, Drug Science, Professor Arthur Christopolous, Professor Chris Langmead (both from Monash University) and from large numbers of clinical, academic and patient groups. Under the rescheduling, current prescribing rights are limited to psychiatrists who have become authorised prescribers under the TGA's Authorised Prescriber Scheme, and psilocybin can only be used for treatment resistant depression and MDMA can only be used for PTSD. This paper reviews the background for this decision, its implications for approvals in other jurisdictions, as well as for the development pathways for other psychedelic drugs. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.", "journal": "British journal of pharmacology", "publication_date": "2026-06-30", "publication_year": 2026, "doi": "10.1111/bph.17398", "pubmed_id": "39701143", "source_url": "https://pubmed.ncbi.nlm.nih.gov/39701143/", "keywords": "3,4-methylenedioxymethamphetamine (MDMA), Australia, psilocybin, psychedelics, therapeutic goods administration (TGA)", "substance_tags": "psilocybin", "source_name": "PubMed", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-02 06:54:10", "raw_json": "{\"pubmed_id\":\"39701143\"}", "topic_tags": "Depression,PTSD,Mechanism of Action,Review Article,Treatment-Resistant Depression", "study_type": "Review Article", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "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": 116, "title": "Exploring new avenues: Psychedelic-assisted therapy for young people.", "normalized_title": "exploring new avenues psychedelic assisted therapy for young people", "authors": "Vamvakopoulou IA, Nicholls D, Nutt DJ, Di Simplicio M.", "abstract": "Rates of mental illness in young people are increasing, whereas the development of novel mental health treatments has not significantly progressed. Psychedelic-assisted therapy, using substances such as psilocybin and 3,4-methylenedioxymethamphetamine (MDMA), has shown potential in the treatment of mental illnesses in the adult population, including depression, anxiety and post-traumatic stress disorder. Interest has been growing around the potential use of psychedelic-assisted therapy to treat mental illness in adolescents. We present here a comprehensive review of all research focusing on children and young people, from experimental research of the 50s to observational and retrospective research focusing on traditional and Western non-medical use. The limited available research so far suggests that psychedelics appear to be safe overall and may have the potential to improve mental wellbeing in young people. However, young people may be at more risk of experiencing anxiety, challenging experiences and ego dissolution, but more thorough clinical research is warranted. Moving forward, we suggest that psychedelic-assisted therapy for young people should be administered within a rigorous ethical framework, where education of both the young people and their families is incorporated. Family involvement should be considered as part of the therapeutic framework. Lastly, avenues within the psychedelic space should be considered for young people, like the use of lower doses (psycholytic approach), which might lower the potential risks that are seen with high doses.", "journal": null, "publication_date": "2026-05-07", "publication_year": 2026, "doi": "10.1002/bcp.70579", "pubmed_id": "42101062", "source_url": "https://doi.org/10.1002/bcp.70579", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-06-30 22:38:07", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"42101062\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,PTSD,Wellbeing,Review Article,Observational Study,Adolescents,Safety", "study_type": "Review Article", "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": 83, "title": "Psilocybin for psychiatric disorders: History, clinical trials, neuroimaging, and regulations.", "normalized_title": "psilocybin for psychiatric disorders history clinical trials neuroimaging and regulations", "authors": "Yonezawa K, Hirata M, Takano H, Kusudo K, Tomiyama S, Harada L, Suzuki K, Nutt DJ, Uchida H, Tani H.", "abstract": "Psilocybin, a classic psychedelic compound, has garnered renewed interest as a potential treatment for various psychiatric disorders. This review provides a comprehensive overview of psilocybin's history, recent clinical evidence, ongoing clinical trials, neuroimaging findings, and regulations. Historically used in spiritual and healing rituals, psilocybin was in the early 1970s subjected to strict legal restrictions that stalled research for decades. However, renewed scientific interest began in the 1990s, with studies demonstrating psilocybin's therapeutic potential for psychiatric disorders. Clinical trials have reported therapeutic effects of psilocybin in major depressive disorder (MDD), depressive symptoms associated with life-threatening illnesses, and in some substance use disorders. Moreover, several phase III clinical trials of psilocybin for depression are currently underway, though trial data for obsessive-compulsive disorder and bipolar depression are limited. Short-term side effects are reportedly generally mild and transient, but long-term effects still need further investigation. Neuroimaging research using magnetic resonance imaging and electroencephalography is still limited and focuses mainly on MDD. However, ongoing clinical trials include neuroimaging studies for psychiatric disorders beyond MDD, as well as positron emission tomography studies for MDD. Regulatory frameworks vary internationally. While many countries continue to classify psilocybin as a prohibited substance, use of psilocybin under controlled conditions is now permitted in Switzerland, parts of the United States, Canada, and Australia. Despite encouraging data, challenges remain, including the need for larger, blinded trials, standardized protocols, and clarification of long-term efficacy and safety. Psilocybin represents a novel therapeutic approach in psychiatric treatment, warranting further rigorous scientific and regulatory research.", "journal": null, "publication_date": "2026-02-25", "publication_year": 2026, "doi": "10.1111/pcn.70042", "pubmed_id": "41749057", "source_url": "https://doi.org/10.1111/pcn.70042", "keywords": "Humans, Hallucinogens, Mental Disorders, Clinical Trials as Topic, Neuroimaging, Psilocybin", "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\":\"41749057\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Addiction,OCD,End-of-Life Distress,Brain Imaging,Aging,Spirituality,Clinical Trial,Review Article,Safety,Adverse Events", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 578, "title": "Perturbing whole-brain models of brain hierarchy: An application for depression following pharmacological treatment.", "normalized_title": "perturbing whole brain models of brain hierarchy an application for depression following pharmacological treatment", "authors": "Socoró-Garrigosa M, Perl YS, Kringelbach ML, Erritzoe D, Nutt DJ, Carhart-Harris R, Vohryzek J, Deco G.", "abstract": "Determining the scale of neural representations is a central challenge in neuroscience. While localized representations have traditionally dominated, evidence suggests information is also encoded in distributed, hierarchical networks. Recent research indicates that the hierarchy of causal influences shaping functional patterns serves as a signature of distinct brain states, with implications for neuropsychiatric disorders. Here, we first explore how whole-brain models, guided by the thermodynamics of mind framework, estimate brain hierarchy and how perturbing such models enables the study of in-silico transitions represented by static functional connectivity. We then apply this to major depressive disorder, where different brain hierarchical reconfigurations emerge following psilocybin and escitalopram treatments. We build resting-state whole-brain models of depressed patients before and after interventions and conduct a dynamic sensitivity analysis to explore brain states' susceptibility-measuring their capacity to change-and their drivability to healthier states. We show that susceptibility is on average reduced by escitalopram and increased by psilocybin, and that both treatments promote healthier transitions. These results align with the post-treatment window of plasticity opened by serotonergic psychedelics and the similar clinical efficacy of both drugs in trials. Overall, this work demonstrates how whole-brain models of brain hierarchy can inform in-silico neurostimulation protocols for neuropsychiatric disorders.", "journal": null, "publication_date": "2025-07-20", "publication_year": 2025, "doi": "10.1111/nyas.15391", "pubmed_id": "40689865", "source_url": "https://doi.org/10.1111/nyas.15391", "keywords": "Brain, Humans, Citalopram, Hallucinogens, Depression, Models, Neurological, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"40689865\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Neuroplasticity", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 584, "title": "The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial.", "normalized_title": "the effects of psilocybin therapy versus escitalopram on cognitive bias a secondary analysis of a randomized controlled trial", "authors": "Henry J, Giribaldi B, Nutt DJ, Erritzoe D, Carhart-Harris R, Lyons T.", "abstract": "BackgroundPatients with Major Depressive Disorder (MDD) have more dysfunctional attitudes than healthy individuals and these pessimistic biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in depression.MethodsSecondary analysis of a two-arm randomized controlled trial assessing the effect of psilocybin therapy versus escitalopram on 'maladaptive' cognitive biases relevant to the construct of depression. Primary outcomes were post-treatment changes in biases at six weeks compared with baseline, as measured using three validated psychological scales.FindingsFifty-nine MDD patients were randomly allocated to the psilocybin (n = 30) or escitalopram (n = 29) groups. Self-reported optimism showed a large increase six-weeks after psilocybin treatment (Mdiff=6·63 p < 0·0001; 95 % CI [4·06, 9·20], d = 1·1), whereas there was no change following escitalopram (Mdiff=1·52, p = 0·205; 95 % CI [-0·59, 3·62], d = 0·4). Behavioral results found that patients were more optimistic about desirable life events after psilocybin treatment (Mdiff=0·16, p = 0·0002; 95 % CI [0·08, 0·23], d = 1·1), but they were also less pessimistic about negative life events after escitalopram treatment (Mdiff=0·07, p = 0·018; 95 % CI [0·01, 0·13], d = 0·5). We found improvements in all three domains of dysfunctional attitudes following psilocybin treatment: achievement (Mdiff=10·37, p < 0·0001; 95 % CI [6·38, 14·53], d = 1·0); dependency (Mdiff=7·97, p < 0·0001; 95 % CI [4·00, 11·93], d = 0·9) and self-control (Mdiff=6·40, p = 0·0006; 95 % CI [2·60, 10·20], d = 0·8)), whereas only the achievement domain improved after escitalopram (Mdiff=4·10, p = 0·005; 95 % CI [1·35, 6·86], d = 0·6).InterpretationThese results suggest that two high-dose sessions with psilocybin therapy are superior to a six-week daily course of a selective serotonin-reuptake inhibitor antidepressant, in remediating negative cognitive biases in depression.", "journal": null, "publication_date": "2025-06-22", "publication_year": 2025, "doi": "10.1016/j.euroneuro.2025.06.003", "pubmed_id": "40554997", "source_url": "https://doi.org/10.1016/j.euroneuro.2025.06.003", "keywords": "Humans, Citalopram, Hallucinogens, Treatment Outcome, Cognition, Psychiatric Status Rating Scales, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"40554997\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Receptor Pharmacology,Randomized Controlled Trial", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 885, "title": "Serotonergic psychedelics for depression: A comprehensive overview.", "normalized_title": "serotonergic psychedelics for depression a comprehensive overview", "authors": "Wingert AM, Agnorelli C, Peill J, Reed S, Nutt DJ, Erritzoe D.", "abstract": "Depressive disorders continue to pose a major clinical challenge worldwide, particularly given the high prevalence and increasing number of treatment-resistant cases. Over the past decade, advances in research have elucidated the antidepressant potential of psilocybin and other 5-HT₂A receptor agonists in patients with major depressive disorder (MDD) and treatment-resistant depression (TRD). Phase I and II clinical trials have consistently demonstrated that even a single administration can yield rapid and sustained symptom reduction. These effects compare favourably with conventional pharmacotherapies such as SSRIs and ketamine. The distinctive pharmacological profile and robust safety data associated with serotonergic psychedelics make them particularly promising candidates, especially for patients who do not respond to standard treatments. Nonetheless, several challenges impede their integration into routine clinical practice, including the resource-intensive nature of psychedelic-assisted therapy, which demands specialized training and controlled settings. Despite those limitations, some countries including Australia, Switzerland or Canada are paving the way by allowing the use of psilocybin in TRD cases. This chapter reviews the antidepressant potential of psilocybin, DMT, ayahuasca and 5-MeO-DMT based on modern clinical trial data, comparing effect sizes of psychedelics to conventional treatments like SSRIs and ketamine, and provides a brief overview of their potential neurobiological mechanisms.", "journal": null, "publication_date": "2025-05-13", "publication_year": 2025, "doi": "10.1016/bs.irn.2025.04.009", "pubmed_id": "40541312", "source_url": "https://doi.org/10.1016/bs.irn.2025.04.009", "keywords": "Animals, Humans, Hallucinogens, Antidepressive Agents, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:04", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"40541312\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Treatment-Resistant Depression,Safety", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 3104, "title": "The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial", "normalized_title": "the effects of psilocybin therapy versus escitalopram on cognitive bias a secondary analysis of a randomized controlled trial", "authors": "Henry J, Giribaldi B, Nutt DJ, Erritzoe D, Carhart-Harris R, Lyons T.", "abstract": "Background Patients with Major Depressive Disorder (MDD) have more dysfunctional attitudes and pessimism than healthy individuals and these biases are correlated with depression severity. Psilocybin has demonstrated sustained remission in MDD. Methods Secondary analysis of a two-arm, randomized controlled trial ( ClinicalTrials.gov Identifier: NCT03429075 ) assessing the effect of psilocybin therapy versus escitalopram on ‘maladaptive’ cognitive biases relevant to the construct of depression. Psilocybin group participants received two 25mg doses and escitalopram group received three weeks of daily 10mg, increased to 20mg for a following three weeks. Primary outcomes in this analysis were post-treatment changes in biases at six weeks compared with baseline, as measured using three validated psychological scales. Findings Fifty-nine MDD patients were randomly allocated to the psilocybin (n=30) or escitalopram (n=29) groups. Self-reported optimism showed a large and significant increase six-weeks after psilocybin treatment ( M diff =6·63 p", "journal": "medRxiv", "publication_date": "2025-03-20", "publication_year": 2025, "doi": "10.1101/2025.03.17.25324123", "pubmed_id": null, "source_url": "https://doi.org/10.1101/2025.03.17.25324123", "keywords": "", "substance_tags": "psilocybin", "source_name": "medRxiv", "date_added": "2026-07-01 11:03:46", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"PPR993220\",\"source\":\"PPR\",\"pub_type\":null,\"publisher\":\"medRxiv\",\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Randomized Controlled Trial", "study_type": "Randomized Controlled Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "preprint" }, { "id": 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": 1267, "title": "Psychedelics: From Cave Art to 21st-Century Medicine for Addiction.", "normalized_title": "psychedelics from cave art to 21st century medicine for addiction", "authors": "Vamvakopoulou IA, Nutt DJ.", "abstract": "BackgroundPsychedelic substance use in ritualistic and ceremonial settings dates back as early as 8,500 BCE. Only in recent years, from the mid-20th century, we have seen the re-emergence of psychedelics in a therapeutic setting and more specifically for the treatment of addiction. This article aims to review research over the past 40 years using classic (psilocybin, lysergic acid diethylamide [LSD], dimethyltryptamine [DMT], mescaline) and atypical (ketamine, ibogaine, 5-MeO-DMT, 3,4-methylenedioxymethamphetamine) psychedelics for the treatment of addiction.SummaryWe will start with an overview of the pharmacology and physiological and psychological properties of psychedelic substances from pre-clinical and clinical research. We will then provide an overview of evidence gathered by studies conducted in controlled research environments and naturalistic and ceremonial settings, while we identify the proposed therapeutic mechanisms of each psychedelic substance.Key messagesClassic and atypical psychedelics show promise as therapeutic alternatives for the treatment of addiction, through the improvement of psychological and physiological symptoms of dependence. A more comprehensive understanding of the ancient and present-day knowledge of the therapeutic potential of psychedelics can facilitate hope for psychedelic therapeutics in the treatment of addiction, especially for individuals who have failed other conventional treatment methods.", "journal": null, "publication_date": "2024-09-24", "publication_year": 2024, "doi": "10.1159/000540062", "pubmed_id": "39321788", "source_url": "https://doi.org/10.1159/000540062", "keywords": "Animals, Humans, Substance-Related Disorders, N,N-Dimethyltryptamine, N-Methyl-3,4-methylenedioxyamphetamine, Mescaline, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Behavior, Addictive, History, Ancient, History, 20th Century, History, 21st Century, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"39321788\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Addiction,Pharmacology,Mechanism of Action,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": 1148, "title": "Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression.", "normalized_title": "effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression", "authors": "Erritzoe D, Barba T, Spriggs MJ, Rosas FE, Nutt DJ, Carhart-Harris R.", "abstract": "BackgroundThere is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling.AimsUsing data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes.MethodsExploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored.Results/outcomesIn the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found.ConclusionDiscontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.", "journal": null, "publication_date": "2024-03-21", "publication_year": 2024, "doi": "10.1177/02698811241237870", "pubmed_id": "38520045", "source_url": "https://doi.org/10.1177/02698811241237870", "keywords": "Humans, Hallucinogens, Treatment Outcome, Drug Therapy, Combination, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"38520045\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Receptor Pharmacology,Wellbeing,Clinical Trial,Safety,Drug Interactions", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1224, "title": "Brain dynamics predictive of response to psilocybin for treatment-resistant depression.", "normalized_title": "brain dynamics predictive of response to psilocybin for treatment resistant depression", "authors": "Vohryzek J, Cabral J, Lord LD, Fernandes HM, Roseman L, Nutt DJ, Carhart-Harris RL, Deco G, Kringelbach ML.", "abstract": "Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here, we leveraged the differential outcome in responders and non-responders to psilocybin (10 and 25 mg, 7 days apart) therapy for depression-to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used large-scale brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a healthy one. Binarizing the sample into treatment responders (>50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-hydroxytryptamine 2a and 5-hydroxytryptamine 1a, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression, and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.", "journal": null, "publication_date": "2024-02-14", "publication_year": 2024, "doi": "10.1093/braincomms/fcae049", "pubmed_id": "38515439", "source_url": "https://doi.org/10.1093/braincomms/fcae049", "keywords": "", "substance_tags": "psilocybin,psilocin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:00", "raw_json": "{\"europe_pmc_id\":\"38515439\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Treatment-Resistant Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1233, "title": "Effects of DMT on mental health outcomes in healthy volunteers.", "normalized_title": "effects of dmt on mental health outcomes in healthy volunteers", "authors": "Timmermann C, Zeifman RJ, Erritzoe D, Nutt DJ, Carhart-Harris RL.", "abstract": "Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin's acute effects (4-6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via 'Oceanic Boundlessness'). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.", "journal": null, "publication_date": "2024-02-06", "publication_year": 2024, "doi": "10.1038/s41598-024-53363-y", "pubmed_id": "38326357", "source_url": "https://doi.org/10.1038/s41598-024-53363-y", "keywords": "Humans, N,N-Dimethyltryptamine, Hallucinogens, Prospective Studies, Healthy Volunteers, Psilocybin, Outcome Assessment, Health Care", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"38326357\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Anxiety,Wellbeing,Observational Study,Healthy Volunteers", "study_type": "Observational Study", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1231, "title": "Psychedelics and sexual functioning: a mixed-methods study.", "normalized_title": "psychedelics and sexual functioning a mixed methods study", "authors": "Barba T, Kettner H, Radu C, Peill JM, Roseman L, Nutt DJ, Erritzoe D, Carhart-Harris R, Giribaldi B.", "abstract": "Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake inhibitors (SSRIs), a first line treatment for depression. The aim of the present paper was to investigate the post-acute effects of psychedelics on self-reported sexual functioning, combining data from two independent studies, one large and naturalistic and the other a smaller but controlled clinical trial. Naturalistic use of psychedelics was associated with improvements in several facets of sexual functioning and satisfaction, including improved pleasure and communication during sex, satisfaction with one's partner and physical appearance. Convergent results were found in a controlled trial of psilocybin therapy versus an SSRI, escitalopram, for depression. In this trial, patients treated with psilocybin reported positive changes in sexual functioning after treatment, while patients treated with escitalopram did not. Despite focusing on different populations and settings, this is the first research study to quantitively investigate the effects of psychedelics on sexual functioning. Results imply a potential positive effect on post-acute sexual functioning and highlight the need for more research on this.", "journal": null, "publication_date": "2024-02-06", "publication_year": 2024, "doi": "10.1038/s41598-023-49817-4", "pubmed_id": "38326446", "source_url": "https://doi.org/10.1038/s41598-023-49817-4", "keywords": "Humans, Hallucinogens, Sexual Behavior, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:04", "raw_json": "{\"europe_pmc_id\":\"38326446\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Receptor Pharmacology,Wellbeing,Clinical Trial,Adverse Events", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 3728, "title": "Neuroimaging in psychedelic drug development: past, present, and future.", "normalized_title": "neuroimaging in psychedelic drug development past present and future", "authors": "Wall MB, Harding R, Zafar R, Rabiner EA, Nutt DJ, Erritzoe D.", "abstract": "Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating psychiatric disorders, including depression, addiction, post-traumatic stress disorder, and potentially others. 'Classic' serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), which have a key locus of action at the 5-HT2A receptor, form the main focus of this movement, but substances including ketamine, 3,4-Methylenedioxymethamphetamine (MDMA) and ibogaine also hold promise. The modern phase of development of these treatment modalities in the early 21st century has occurred concurrently with the wider use of advanced human neuroscientific research methods; principally neuroimaging. This can potentially enable assessment of drug and therapy brain effects with greater precision and quantification than any previous novel development in psychiatric pharmacology. We outline the major trends in existing data and suggest the modern development of PT has benefitted greatly from the use of neuroimaging. Important gaps in existing knowledge are identified, namely: the relationship between acute drug effects and longer-term (clinically-relevant) effects, the precise characterisation of effects at the 5-HT2A receptor and relationships with functional/clinical effects, and the possible impact of these compounds on neuroplasticity. A road-map for future research is laid out, outlining clinical studies which will directly address these three questions, principally using combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods, plus other adjunct techniques. Multimodal (PET/MRI) studies using modern PET techniques such as the 5-HT2A-selective ligand [11 C]Cimbi-36 (and other ligands sensitive to neuroplasticity changes) alongside MRI measures of brain function would provide a 'molecular-functional-clinical bridge' in understanding. Such results would help to resolve some of these questions and provide a firmer foundation for the ongoing development of PT.", "journal": null, "publication_date": "2023-09-26", "publication_year": 2023, "doi": "10.1038/s41380-023-02271-0", "pubmed_id": "37759038", "source_url": "https://doi.org/10.1038/s41380-023-02271-0", "keywords": "Humans, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2A, Hallucinogens, Neuroimaging, Psilocybin", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:08:42", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"37759038\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,PTSD,Addiction,Neuroplasticity,Brain Imaging,Pharmacology,Receptor Pharmacology,Aging", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1390, "title": "Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: A systematic review and individual participant data meta-analysis.", "normalized_title": "assessing the risk of symptom worsening in psilocybin assisted therapy for depression a systematic review and individual participant data meta analysis", "authors": "Simonsson O, Carlbring P, Carhart-Harris R, Davis AK, Nutt DJ, Griffiths RR, Erritzoe D, Goldberg SB.", "abstract": "We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies.", "journal": null, "publication_date": "2023-07-22", "publication_year": 2023, "doi": "10.1016/j.psychres.2023.115349", "pubmed_id": "37523886", "source_url": "https://doi.org/10.1016/j.psychres.2023.115349", "keywords": "Humans, Hallucinogens, Sample Size, Depression, Symptom Flare Up, Psilocybin, Escitalopram", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"37523886\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Meta-Analysis,Systematic Review,Review Article,Safety", "study_type": "Meta-Analysis", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1293, "title": "Personality Change in a Trial of Psilocybin Therapy vs Escitalopram Treatment for Depression - CORRIGENDUM.", "normalized_title": "personality change in a trial of psilocybin therapy vs escitalopram treatment for depression corrigendum", "authors": "Weiss B, Ginige I, Shannon L, Giribaldi B, Murphy-Beiner A, Murphy R, Baker-Jones M, Martell J, Nutt DJ, Carhart-Harris RL, Erritzoe D.", "abstract": "", "journal": null, "publication_date": "2023-07-18", "publication_year": 2023, "doi": "10.1017/s0033291723002039", "pubmed_id": "37466289", "source_url": "https://doi.org/10.1017/s0033291723002039", "keywords": "Humans, Citalopram, Hallucinogens, Depression, Personality, Personality Disorders, Psilocybin, Escitalopram", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:05", "raw_json": "{\"europe_pmc_id\":\"37466289\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Personality Change", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 1330, "title": "Cost-effectiveness of psilocybin-assisted therapy for severe depression: exploratory findings from a decision analytic model.", "normalized_title": "cost effectiveness of psilocybin assisted therapy for severe depression exploratory findings from a decision analytic model", "authors": "McCrone P, Fisher H, Knight C, Harding R, Schlag AK, Nutt DJ, Neill JC.", "abstract": "BackgroundThere is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT.MethodsA decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates.ResultsThe expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective.ConclusionsPsilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base.", "journal": null, "publication_date": "2023-06-01", "publication_year": 2023, "doi": "10.1017/s0033291723001411", "pubmed_id": "37264950", "source_url": "https://doi.org/10.1017/s0033291723001411", "keywords": "Humans, Depression, Psychotherapy, Quality-Adjusted Life Years, Cost-Benefit Analysis, 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\":\"37264950\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 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": 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": 3730, "title": "A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression.", "normalized_title": "a bayesian reanalysis of a trial of psilocybin versus escitalopram for depression", "authors": "Nayak SM, Bari BA, Yaden DB, Spriggs MJ, Rosas FE, Peill JM, Giribaldi B, Erritzoe D, Nutt DJ, Carhart-Harris R.", "abstract": "ObjectivesTo perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis.DesignReanalysis of a two-arm double-blind placebo controlled trial.ParticipantsFifty-nine patients with MDD.InterventionsTwo doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups.Outcome measuresQuick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A.ResultsUsing Bayes factors and 'skeptical priors' which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a 'clinically meaningful amount' (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin's non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis.ConclusionsThis Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful--and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respect to current leading treatments.Trial registration numberNCT03429075.", "journal": null, "publication_date": "2022-10-27", "publication_year": 2022, "doi": "10.1089/psymed.2022.0002", "pubmed_id": "37337526", "source_url": "https://doi.org/10.1089/psymed.2022.0002", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 11:08:42", "last_checked": "2026-07-01 11:22:01", "raw_json": "{\"europe_pmc_id\":\"37337526\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression", "study_type": "Other", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 1605, "title": "Mescaline: The forgotten psychedelic.", "normalized_title": "mescaline the forgotten psychedelic", "authors": "Vamvakopoulou IA, Narine KAD, Campbell I, Dyck JRB, Nutt DJ.", "abstract": "IntroductionMescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, research on mescaline and other classical psychedelics has been limited.ObjectivesThis article aims to review the pharmacology and behavioural effects of mescaline, focusing on preclinical and clinical research.FindingsMescaline is a serotonin 5HT2A/2C receptor agonist, with its main hallucinogenic effects being mediated via its 5HT2A receptor agonist action. It also exerts effects via agonist binding at α1A/2A noradrenaline and D1/2/3 dopamine receptors. Overall, mescaline has anxiolytic-like effects in animals and increases prosocial behaviour, locomotion, and response reactivity. In humans, mescaline can induce euphoria, hallucinations, improvements in well-being and mental health conditions, and psychotomimetic effects in a naturalistic or religious setting.ConclusionThe pharmacological mechanisms of mescaline are similar to those of other classical psychedelics, like psilocybin and lysergic acid diethylamide (LSD). Mescaline appears to be safe to consume, with most intoxications being mild and easily treatable. Improvement in mental well-being and its ability to overcome alcoholism render mescaline potentially beneficial in clinical settings. This article is part of the Special Issue on 'Psilocybin Research'.", "journal": null, "publication_date": "2022-10-13", "publication_year": 2022, "doi": "10.1016/j.neuropharm.2022.109294", "pubmed_id": "36252614", "source_url": "https://doi.org/10.1016/j.neuropharm.2022.109294", "keywords": "Animals, Humans, Memory Disorders, Mescaline, Lysergic Acid Diethylamide, 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 11:22:05", "raw_json": "{\"europe_pmc_id\":\"36252614\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Pharmacology,Mechanism of Action,Receptor Pharmacology,Wellbeing,Review Article,Animal Study", "study_type": "Review Article", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 1698, "title": "Effects of psilocybin versus escitalopram on rumination and thought suppression in depression.", "normalized_title": "effects of psilocybin versus escitalopram on rumination and thought suppression in depression", "authors": "Barba T, Buehler S, Kettner H, Radu C, Cunha BG, Nutt DJ, Erritzoe D, Roseman L, Carhart-Harris R.", "abstract": "BackgroundMajor depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression.AimsTo assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive disorder.MethodBased on data derived from a randomised clinical trial (N = 59), we performed exploratory analyses on the impact of escitalopram versus psilocybin (i.e. condition) on rumination and thought suppression from 1 week before to 6 weeks after treatment inception (i.e. time), using mixed analysis of variance. Condition responder versus non-responder subgroup analyses were also done, using the standard definition of ≥50% symptom reduction.ResultsA time×condition interaction was found for rumination (F(1, 56) = 4.58, P = 0.037) and thought suppression (F(1,57) = 5.88, P = 0.019), with post hoc tests revealing significant decreases exclusively in the psilocybin condition. When analysing via response, a significant time×condition×response interaction for thought suppression (F(1,54) = 8.42, P = 0.005) and a significant time×response interaction for rumination (F(1,54) = 23.50, P < 0.001) were evident. Follow-up tests revealed that decreased thought suppression was exclusive to psilocybin responders, whereas rumination decreased in both responder groups. In the psilocybin arm, decreases in rumination and thought suppression correlated with ego dissolution and session-linked psychological insight.ConclusionsThese data provide further evidence on the therapeutic mechanisms of psilocybin and escitalopram in the treatment of depression.", "journal": null, "publication_date": "2022-09-05", "publication_year": 2022, "doi": "10.1192/bjo.2022.565", "pubmed_id": "36065128", "source_url": "https://doi.org/10.1192/bjo.2022.565", "keywords": "", "substance_tags": "psilocybin", "source_name": "Europe PMC", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:22:02", "raw_json": "{\"europe_pmc_id\":\"36065128\",\"source\":\"MED\",\"pub_type\":null,\"publisher\":null,\"importer\":\"Europe PMC\"}", "topic_tags": "Depression,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Drug Interactions", "study_type": "Clinical Trial", "hidden": 0, "false_positive": 0, "curation_notes": null, "merged_into_id": null, "curation_locked": 0, "publication_status": "published" }, { "id": 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": 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": 1815, "title": "Adverse effects of psychedelics: From anecdotes and misinformation to systematic science.", "normalized_title": "adverse effects of psychedelics from anecdotes and misinformation to systematic science", "authors": "Schlag AK, Aday J, Salam I, Neill JC, Nutt DJ", "abstract": "Despite an increasing body of research highlighting their efficacy to treat a broad range of medical conditions, psychedelic drugs remain a controversial issue among the public and politicians, tainted by previous stigmatisation and perceptions of risk and danger. This narrative review examines the evidence for potential harms of the classic psychedelics by separating anecdotes and misinformation from systematic research. Taking a high-level perspective, we address both psychological and psychiatric risks, such as abuse liability and potential for dependence, as well as medical harms, including toxicity and overdose. We explore the evidence base for these adverse effects to elucidate which of these harms are based largely on anecdotes versus those that stand up to current scientific scrutiny. Our review shows that medical risks are often minimal, and that many - albeit not all - of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence, with the majority of reported adverse effects not being observed in a regulated and/or medical context. This highlights the importance for clinicians and therapists to keep to the highest safety and ethical standards. It is imperative not to be overzealous and to ensure balanced media reporting to avoid future controversies, so that much needed research can continue.", "journal": "Journal of psychopharmacology (Oxford, England)", "publication_date": "2022-02-28", "publication_year": 2022, "doi": "10.1177/02698811211069100", "pubmed_id": "35107059", "source_url": "https://pubmed.ncbi.nlm.nih.gov/35107059/", "keywords": "Psilocybin, abuse liability/dependence, ayahuasca, d-lysergic acid diethylamide, dimethyltryptamine, hallucinogen persistent perception disorder, hypertension, mescaline, toxicity", "substance_tags": "psilocybin", "source_name": "PubMed", "date_added": "2026-07-01 06:48:05", "last_checked": "2026-07-01 11:20:39", "raw_json": "{\"pubmed_id\":\"35107059\"}", "topic_tags": "Review Article,Healthcare Workers,Safety,Toxicity,Abuse Liability", "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" } ] }