{"topic":"psychiatric-therapeutics","sort":"top","limit":25,"offset":0,"count":25,"papers":[{"id":"doi:10.1177/0269881116675513","kind":"article","title":"Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial","authors":["Roland R. Griffiths","Matthew W. Johnson","Michael Anthony Carducci","Annie Umbricht","William A. Richards","Brian D. Richards","Mary P Cosimano","Margaret A. Klinedinst"],"author_count":8,"year":2016,"published":"2016-11-30","venue":"Journal of Psychopharmacology","cited_by":2200,"doi":"10.1177/0269881116675513","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1177/0269881116675513","archive_url":"https://space-kitty.com/papers/doi:10.1177/0269881116675513","updated":null,"pmid":"27909165","pmcid":"PMC5367557","openalex_id":"W2558412547","pdf_url":"https://journals.sagepub.com/doi/pdf/10.1177/0269881116675513","abstract":"Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00465595.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial\" by Roland R. Griffiths, Matthew W. Johnson, Michael Anthony Carducci et al., https://doi.org/10.1177/0269881116675513, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1056/nejmoa2032994","kind":"article","title":"Trial of Psilocybin versus Escitalopram for Depression","authors":["Robin Lester Carhart-Harris","Bruna Giribaldi","Rosalind Watts","Michelle Baker-Jones","Ashleigh Murphy-Beiner","Roberta Murphy","Jonny Martell","Allan Blemings","David Erritzøe","David Nutt"],"author_count":10,"year":2021,"published":"2021-04-14","venue":"New England Journal of Medicine","cited_by":1390,"doi":"10.1056/nejmoa2032994","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1056/nejmoa2032994","archive_url":"https://space-kitty.com/papers/doi:10.1056/nejmoa2032994","updated":null,"pmid":"33852780","pmcid":null,"openalex_id":"W3156937150","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1177/0269881116675512","kind":"article","title":"Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial","authors":["Stephen Ross","Anthony P. Bossis","Jeffrey R. Guss","Gabrielle Agin-Liebes","Tara C. Malone","Barry H Cohen","Sarah E. Mennenga","Alexander Belser","Krystallia Kalliontzi","James S. Babb","Zhe Su","Patricia M A Corby","Brian L. Schmidt"],"author_count":13,"year":2016,"published":"2016-11-30","venue":"Journal of Psychopharmacology","cited_by":1697,"doi":"10.1177/0269881116675512","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1177/0269881116675512","archive_url":"https://space-kitty.com/papers/doi:10.1177/0269881116675512","updated":null,"pmid":"27909164","pmcid":"PMC5367551","openalex_id":"W2559739670","pdf_url":"https://journals.sagepub.com/doi/pdf/10.1177/0269881116675512","abstract":"BACKGROUND: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. METHODS: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. RESULTS: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. CONCLUSIONS: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00957359.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial\" by Stephen Ross, Anthony P. Bossis, Jeffrey R. Guss et al., https://doi.org/10.1177/0269881116675512, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1056/nejmoa2206443","kind":"article","title":"Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression","authors":["Guy M. Goodwin","Scott T. Aaronson","Oscar Alvarez","Peter C. Arden","Annie Baker","James C. Bennett","Catherine Bird","Renske E. Blom","Christine Brennan","Donna Brusch","Lisa Burke","Kete Campbell‐Coker","Robin Lester Carhart-Harris","Joseph Cattell","Aster Daniel","Charles DeBattista","Boadie Waid Dunlop","Katherine Eisen","David Feifel","MacKenzie Forbes","Hannah M. Haumann","David J. Hellerstein","Astrid I. Hoppe","Muhammad Ishrat Husain","Luke A. Jelen"],"author_count":74,"year":2022,"published":"2022-11-02","venue":"New England Journal of Medicine","cited_by":1166,"doi":"10.1056/nejmoa2206443","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1056/nejmoa2206443","archive_url":"https://space-kitty.com/papers/doi:10.1056/nejmoa2206443","updated":null,"pmid":"36322843","pmcid":null,"openalex_id":"W4308146982","pdf_url":"https://www.nejm.org/doi/pdf/10.1056/NEJMoa2206443?articleTools=true","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1016/s2215-0366(16)30065-7","kind":"article","title":"Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study","authors":["Robin Lester Carhart-Harris","Mark Bolstridge","James Rucker","Camilla Day","David Erritzøe","Mendel Kaelen","Michael Bloomfield","James A Rickard","Ben Forbes","Amanda Feilding","David M. Taylor","Steve Pilling","Valerie H. Curran","David Nutt"],"author_count":14,"year":2016,"published":"2016-05-17","venue":"The Lancet Psychiatry","cited_by":1538,"doi":"10.1016/s2215-0366(16)30065-7","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/s2215-0366(16)30065-7","archive_url":"https://space-kitty.com/papers/doi:10.1016/s2215-0366(16)30065-7","updated":null,"pmid":"27210031","pmcid":null,"openalex_id":"W2396675581","pdf_url":"http://www.thelancet.com/article/S2215036616300657/pdf","abstract":"BACKGROUND: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. METHODS: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. FINDINGS: Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference -11·8, 95% CI -9·15 to -14·35, p=0·002, Hedges' g=3·1) and 3 months (-9·2, 95% CI -5·69 to -12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted. INTERPRETATION: This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach. FUNDING: Medical Research Council.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study\" by Robin Lester Carhart-Harris, Mark Bolstridge, James Rucker et al., https://doi.org/10.1016/s2215-0366(16)30065-7, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1001/jamapsychiatry.2020.3285","kind":"article","title":"Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder","authors":["Alan K. Davis","Frederick Streeter Barrett","Darrick G. May","Mary P Cosimano","Nathan D. Sepeda","Matthew W. Johnson","Patrick H. Finan","Roland R. Griffiths"],"author_count":8,"year":2020,"published":"2020-11-04","venue":"JAMA Psychiatry","cited_by":1300,"doi":"10.1001/jamapsychiatry.2020.3285","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1001/jamapsychiatry.2020.3285","archive_url":"https://space-kitty.com/papers/doi:10.1001/jamapsychiatry.2020.3285","updated":null,"pmid":"33146667","pmcid":"PMC7643046","openalex_id":"W3096208965","pdf_url":"https://jamanetwork.com/journals/jamapsychiatry/articlepdf/2772630/jamapsychiatry_davis_2020_oi_200060_1619663147.19801.pdf","abstract":"Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. Objective: To investigate the effect of psilocybin therapy in patients with MDD. Design, Setting, and Participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population). Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay. Main Outcomes and Measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR). Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score). Conclusions and Relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression. Trial Registration: ClinicalTrials.gov Identifier: NCT03181529.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder\" by Alan K. Davis, Frederick Streeter Barrett, Darrick G. May et al., https://doi.org/10.1001/jamapsychiatry.2020.3285, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1001/archgenpsychiatry.2010.116","kind":"article","title":"Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer","authors":["Charles S. Grob","Alicia L. Danforth","Gurpreet S Chopra","Marycie Hagerty","Charles R. McKay","Adam L. Halberstadt","George R. Greer"],"author_count":7,"year":2010,"published":"2010-09-06","venue":"Archives of General Psychiatry","cited_by":1205,"doi":"10.1001/archgenpsychiatry.2010.116","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1001/archgenpsychiatry.2010.116","archive_url":"https://space-kitty.com/papers/doi:10.1001/archgenpsychiatry.2010.116","updated":null,"pmid":"20819978","pmcid":null,"openalex_id":"W2161555895","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1007/s00213-017-4771-x","kind":"article","title":"Psilocybin with psychological support for treatment-resistant depression: six-month follow-up","authors":["Robin Lester Carhart-Harris","Mark Bolstridge","Camilla Day","James Rucker","Rhianna Watts","David Erritzøe","Mendel Kaelen","Bruna Giribaldi","Michael Bloomfield","Stephen Pilling","J. A. Rickard","Benjamin Forbes","Amanda Feilding","David M. Taylor","H. Valerie Curran","David Nutt"],"author_count":16,"year":2017,"published":"2017-11-08","venue":"Psychopharmacology","cited_by":970,"doi":"10.1007/s00213-017-4771-x","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1007/s00213-017-4771-x","archive_url":"https://space-kitty.com/papers/doi:10.1007/s00213-017-4771-x","updated":null,"pmid":"29119217","pmcid":"PMC5813086","openalex_id":"W2767530231","pdf_url":"https://link.springer.com/content/pdf/10.1007/s00213-017-4771-x.pdf","abstract":"RATIONALE: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. OBJECTIVES: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. METHODS: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. RESULTS: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. CONCLUSIONS: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Psilocybin with psychological support for treatment-resistant depression: six-month follow-up\" by Robin Lester Carhart-Harris, Mark Bolstridge, Camilla Day et al., https://doi.org/10.1007/s00213-017-4771-x, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1001/jama.2023.14530","kind":"article","title":"Single-Dose Psilocybin Treatment for Major Depressive Disorder","authors":["Charles L. Raison","Gerard Sanacora","Joshua D. Woolley","Keith G. Heinzerling","Boadie Waid Dunlop","Randall Brown","Rishi Kakar","Michael Hassman","Rupal Trivedi","Reid J. Robison","Natalie Gukasyan","Sandeep Manel Nayak","Xiaojue Hu","Kelley C. O’Donnell","Benjamin Kelmendi","Jordan Sloshower","Andrew Penn","Ellen Bradley","Daniel F. Kelly","Tanja Mletzko","Christopher R. N. Nicholas","Paul R. Hutson","Gary Tarpley","Malynn L. Utzinger-Wheeler","Kelsey Lenoch"],"author_count":35,"year":2023,"published":"2023-08-31","venue":"JAMA","cited_by":544,"doi":"10.1001/jama.2023.14530","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1001/jama.2023.14530","archive_url":"https://space-kitty.com/papers/doi:10.1001/jama.2023.14530","updated":null,"pmid":"37651119","pmcid":null,"openalex_id":"W4386305655","pdf_url":"https://jamanetwork.com/journals/jama/articlepdf/2808950/jama_raison_2023_oi_230092_1693922877.34626.pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1124/pr.118.017160","kind":"review","title":"REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics","authors":["Carhart-Harris RL","Friston KJ"],"author_count":2,"year":2019,"published":"2019-07-01","venue":"Pharmacological reviews","cited_by":711,"doi":"10.1124/pr.118.017160","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1124/pr.118.017160","archive_url":"https://space-kitty.com/papers/doi:10.1124/pr.118.017160","updated":null,"pmid":"31221820","pmcid":"PMC6588209","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6588209/pdf","abstract":"This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that-via their entropic effect on spontaneous cortical activity-psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system. We assemble evidence for this model and show how it can explain a broad range of phenomena associated with the psychedelic experience. With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors. We end by discussing further implications of the model, such as that psychedelics can bring about the revision of other heavily weighted high-level priors, not directly related to mental health, such as those underlying partisan and/or overly-confident political, religious, and/or philosophical perspectives. SIGNIFICANCE STATEMENT: Psychedelics are capturing interest, with efforts underway to bring psilocybin therapy to marketing authorisation and legal access within a decade, spearheaded by the findings of a series of phase 2 trials. In this climate, a compelling unified model of how psychedelics alter brain function to alter consciousness would have appeal. Towards this end, we have sought to integrate a leading model of global brain function, hierarchical predictive coding , with an often-cited model of the acute action of psychedelics, the entropic brain hypothesis . The resulting synthesis states that psychedelics work to relax high-level priors, sensitising them to liberated bottom-up information flow, which, with the right intention, care provision and context, can help guide and cultivate the revision of entrenched pathological priors.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics\" by Carhart-Harris RL, Friston KJ, https://doi.org/10.1124/pr.118.017160, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.3389/fphar.2017.00974","kind":"article","title":"Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression","authors":["Leor Roseman","David Nutt","Robin Lester Carhart-Harris"],"author_count":3,"year":2018,"published":"2018-01-17","venue":"Frontiers in Pharmacology","cited_by":808,"doi":"10.3389/fphar.2017.00974","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.3389/fphar.2017.00974","archive_url":"https://space-kitty.com/papers/doi:10.3389/fphar.2017.00974","updated":null,"pmid":"29387009","pmcid":"PMC5776504","openalex_id":"W2792444257","pdf_url":"https://www.frontiersin.org/articles/10.3389/fphar.2017.00974/pdf","abstract":"Introduction: It is a basic principle of the ‘psychedelic’ treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would not. Material and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10mg and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-time and DED-by-time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson’s correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. More specifically, future therapeutic work with psychedelics may consider investigating ways which enhance mystical-type experience and reduce anxiety, given the growing evidence that this serves the efficacy of the treatment model.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression\" by Leor Roseman, David Nutt, Robin Lester Carhart-Harris, https://doi.org/10.3389/fphar.2017.00974, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.3389/fnhum.2014.00020","kind":"article","title":"The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs","authors":["Carhart-Harris RL","Leech R","Hellyer PJ","Shanahan M","Feilding A","Tagliazucchi E","Chialvo DR","Nutt D"],"author_count":8,"year":2014,"published":"2014-02-03","venue":"Frontiers in human neuroscience","cited_by":716,"doi":"10.3389/fnhum.2014.00020","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.3389/fnhum.2014.00020","archive_url":"https://space-kitty.com/papers/doi:10.3389/fnhum.2014.00020","updated":null,"pmid":"24550805","pmcid":"PMC3909994","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC3909994/pdf","abstract":"Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of \"primary states\" is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit \"criticality,\" i.e., the property of being poised at a \"critical\" point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs\" by Carhart-Harris RL, Leech R, Hellyer PJ et al., https://doi.org/10.3389/fnhum.2014.00020, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1001/jamapsychiatry.2022.2096","kind":"article","title":"Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial","authors":["Bogenschutz MP","Ross S","Bhatt S","Baron T","Forcehimes AA","Laska E","Mennenga SE","O'Donnell K","Owens LT","Podrebarac S","Rotrosen J","Tonigan JS","Worth L"],"author_count":13,"year":2022,"published":"2022-10-01","venue":"JAMA psychiatry","cited_by":504,"doi":"10.1001/jamapsychiatry.2022.2096","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1001/jamapsychiatry.2022.2096","archive_url":"https://space-kitty.com/papers/doi:10.1001/jamapsychiatry.2022.2096","updated":null,"pmid":"36001306","pmcid":"PMC9403854","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC9403854/pdf","abstract":"Importance Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown. Objective To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy. Design, setting, and participants In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following the first dose of study medication. The study was conducted at 2 academic centers in the US. Participants were recruited from the community between March 12, 2014, and March 19, 2020. Adults aged 25 to 65 years with a DSM-IV diagnosis of alcohol dependence and at least 4 heavy drinking days during the 30 days prior to screening were included. Exclusion criteria included major psychiatric and drug use disorders, hallucinogen use, medical conditions that contraindicated the study medications, use of exclusionary medications, and current treatment for AUD. Interventions Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy. Main outcomes and measures The primary outcome was percentage of heavy drinking days, assessed using a timeline followback interview, contrasted between groups over the 32-week period following the first administration of study medication using multivariate repeated-measures analysis of variance. Results A total of 95 participants (mean [SD] age, 46 [12] years; 42 [44.2%] female) were randomized (49 to psilocybin and 46 to diphenhydramine). One participant (1.1%) was American Indian/Alaska Native, 3 (3.2%) were Asian, 4 (4.2%) were Black, 14 (14.7%) were Hispanic, and 75 (78.9%) were non-Hispanic White. Of the 95 randomized participants, 93 received at least 1 dose of study medication and were included in the primary outcome analysis. Percentage of heavy drinking days during the 32-week double-blind period was 9.7% for the psilocybin group and 23.6% for the diphenhydramine group, a mean difference of 13.9%; (95% CI, 3.0-24.7; F1,86 = 6.43; P = .01). Mean daily alcohol consumption (number of standard drinks per day) was also lower in the psilocybin group. There were no serious adverse events among participants who received psilocybin. Conclusions and relevance Psilocybin administered in combination with psychotherapy produced robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy. These results provide support for further study of psilocybin-assisted treatment for AUD. Trial registration ClinicalTrials.gov Identifier: NCT02061293.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial\" by Bogenschutz MP, Ross S, Bhatt S et al., https://doi.org/10.1001/jamapsychiatry.2022.2096, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1176/appi.ajp.2019.19010035","kind":"review","title":"Psychedelics and Psychedelic-Assisted Psychotherapy","authors":["Collin M. Reiff","Elon E. Richman","Charles B. Nemeroff","Linda L. Carpenter","Alik S. Widge","Carolyn I. Rodríguez","Ned H. Kalin","William Maffitt McDonald"],"author_count":8,"year":2020,"published":"2020-02-26","venue":"American Journal of Psychiatry","cited_by":649,"doi":"10.1176/appi.ajp.2019.19010035","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1176/appi.ajp.2019.19010035","archive_url":"https://space-kitty.com/papers/doi:10.1176/appi.ajp.2019.19010035","updated":null,"pmid":"32098487","pmcid":null,"openalex_id":"W3006905788","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/npp.2017.84","kind":"review","title":"The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future","authors":["Robin Lester Carhart-Harris","Guy M. Goodwin"],"author_count":2,"year":2017,"published":"2017-04-26","venue":"Neuropsychopharmacology","cited_by":703,"doi":"10.1038/npp.2017.84","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/npp.2017.84","archive_url":"https://space-kitty.com/papers/doi:10.1038/npp.2017.84","updated":null,"pmid":"28443617","pmcid":null,"openalex_id":"W2610144880","pdf_url":"https://www.nature.com/articles/npp201784.pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41591-022-01744-z","kind":"article","title":"Increased global integration in the brain after psilocybin therapy for depression","authors":["Richard E. Daws","Christopher Timmermann","Bruna Giribaldi","James D. Sexton","Matthew B. Wall","David Erritzøe","Leor Roseman","David Nutt","Robin Lester Carhart-Harris"],"author_count":9,"year":2022,"published":"2022-04-01","venue":"Nature Medicine","cited_by":443,"doi":"10.1038/s41591-022-01744-z","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41591-022-01744-z","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41591-022-01744-z","updated":null,"pmid":"35411074","pmcid":null,"openalex_id":"W4223491164","pdf_url":"https://www.researchsquare.com/article/rs-513323/latest.pdf","abstract":null,"abstract_license":null,"license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"arxiv:1405.6466","kind":"article","title":"Enhanced repertoire of brain dynamical states during the psychedelic experience","authors":["Enzo Tagliazucchi","Robin Carhart-Harris","Robert Leech","David Nutt","Dante R. Chialvo"],"author_count":5,"year":2014,"published":"2014-05-26","venue":"Hum. Brain Mapp., 35: 5442-5456, 2014","cited_by":398,"doi":"10.1002/hbm.22562","arxiv_id":"1405.6466","nct_id":null,"source_url":"https://arxiv.org/abs/1405.6466","archive_url":"https://space-kitty.com/papers/arxiv:1405.6466","updated":"2014-05-26","pmid":null,"pmcid":null,"openalex_id":"W2170596036","pdf_url":"https://arxiv.org/pdf/1405.6466","abstract":"The study of rapid changes in brain dynamics and functional connectivity (FC) is of increasing interest in neuroimaging. Brain states departing from normal waking consciousness are expected to be accompanied by alterations in the aforementioned dynamics. In particular, the psychedelic experience produced by psilocybin (a substance found in `magic mushrooms`) is characterized by unconstrained cognition and profound alterations in the perception of time, space and selfhood. Considering the spontaneous and subjective manifestation of these effects, we hypothesize that neural correlates of the psychedelic experience can be found in the dynamics and variability of spontaneous brain activity fluctuations and connectivity, measurable with functional Magnetic Resonance Imaging (fMRI). Fifteen healthy subjects were scanned before, during and after intravenous infusion of psilocybin and an inert placebo. Blood-Oxygen Level Dependent (BOLD) temporal variability was assessed computing the variance and total spectral power, resulting in increased signal variability bilaterally in the hippocampi and anterior cingulate cortex. Changes in BOLD signal spectral behavior (including spectral scaling exponents) affected exclusively higher brain systems such as the default mode, executive control and dorsal attention networks. A novel framework enabled us to track different connectivity states explored by the brain during rest. This approach revealed a wider repertoire of connectivity states post-psilocybin than during control conditions. Together, the present results provide a comprehensive account of the effects of psilocybin on dynamical behaviour in the human brain at a macroscopic level and may have implications for our understanding of the unconstrained, hyper-associative quality of consciousness in the psychedelic state.","abstract_license":"CC0-1.0 (arXiv descriptive metadata)","license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["q-bio.NC"],"details":null,"provenance":"arxiv","attribution":"Abstract: arXiv descriptive metadata (CC0). Thank you to arXiv for use of its open access interoperability. This service was not reviewed or approved by, nor does it necessarily express or reflect the policies or opinions of, arXiv."},{"id":"doi:10.1177/0022167817709585","kind":"article","title":"Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression","authors":["Rosalind Watts","Camilla Day","Jacob Krzanowski","David Nutt","Robin Lester Carhart-Harris"],"author_count":5,"year":2017,"published":"2017-06-19","venue":"Journal of Humanistic Psychology","cited_by":586,"doi":"10.1177/0022167817709585","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1177/0022167817709585","archive_url":"https://space-kitty.com/papers/doi:10.1177/0022167817709585","updated":null,"pmid":null,"pmcid":null,"openalex_id":"W2644260506","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.2147/ndt.s198774","kind":"review","title":"Management of Treatment-Resistant Depression: Challenges and Strategies","authors":["Daphne Voineskos","Zafiris Jeff Daskalakis","Daniel M. Blumberger"],"author_count":3,"year":2020,"published":"2020-01-01","venue":"Neuropsychiatric Disease and Treatment","cited_by":446,"doi":"10.2147/ndt.s198774","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.2147/ndt.s198774","archive_url":"https://space-kitty.com/papers/doi:10.2147/ndt.s198774","updated":null,"pmid":"32021216","pmcid":null,"openalex_id":"W3000386776","pdf_url":"https://www.dovepress.com/getfile.php?fileID=55553","abstract":null,"abstract_license":null,"license":"cc-by-nc","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Treatment of Major Depression"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/tp.2015.136","kind":"article","title":"R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects","authors":["Yang C","Shirayama Y","Zhang JC","Ren Q","Yao W","Ma M","Dong C","Hashimoto K"],"author_count":8,"year":2015,"published":"2015-09-01","venue":"Translational psychiatry","cited_by":493,"doi":"10.1038/tp.2015.136","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/tp.2015.136","archive_url":"https://space-kitty.com/papers/doi:10.1038/tp.2015.136","updated":null,"pmid":"26327690","pmcid":"PMC5068814","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5068814/pdf","abstract":"Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)-TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF-TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF-TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects\" by Yang C, Shirayama Y, Zhang JC et al., https://doi.org/10.1038/tp.2015.136, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1016/j.eclinm.2022.101809","kind":"article","title":"Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial","authors":["Robin von Rotz","Eva Maria Schindowski","Johannes Jungwirth","Anna Schuldt","Nathalie M. Rieser","Katharina Zahoranszky","Erich Seifritz","Albina Nowak","Peter Nowak","Lutz Jäncke","Katrin H. Preller","Franz X. Vollenweider"],"author_count":12,"year":2022,"published":"2022-12-28","venue":"EClinicalMedicine","cited_by":354,"doi":"10.1016/j.eclinm.2022.101809","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.eclinm.2022.101809","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.eclinm.2022.101809","updated":null,"pmid":"36636296","pmcid":"PMC9830149","openalex_id":"W4313530670","pdf_url":"https://europepmc.org/articles/PMC9830149/pdf","abstract":"Background: Psilocybin has been suggested as a novel, rapid-acting treatment for depression. Two consecutive doses have been shown to markedly decrease symptom severity in an open-label setting or when compared to a waiting list group. To date, to our knowledge, no other trial compared a single, moderate dose of psilocybin to a placebo condition. Methods: In this double-blind, randomised clinical trial, 52 participants diagnosed with major depressive disorder and no unstable somatic conditions were allocated to receive either a single, moderate dose (0.215 mg/kg body weight) of psilocybin or placebo in conjunction with psychological support. MADRS and BDI scores were assessed to estimate depression severity, while changes from baseline to 14 days after the intervention were defined as primary endpoints. The trial took place between April 11th, 2019 and October 12th, 2021 at the psychiatric university hospital in Zürich, Switzerland and was registered with clinicaltrials.gov (NCT03715127). Findings: = 0.67; P = 0.019; BDI) 14 days after the intervention. 14/26 (54%) participants met the MADRS remission criteria in the psilocybin condition. Interpretation: These results suggest that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to a placebo condition for at least two weeks. No serious adverse events were recorded. Larger, multi-centric trials with longer follow-up periods are needed to inform further optimisation of this novel treatment paradigm. Funding: The study was funded by the Swiss National Science Foundation, Crowdfunding, the Swiss Neuromatrix Foundation, and the Heffter Research Institute.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Psychedelics and Drug Studies"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial\" by Robin von Rotz, Eva Maria Schindowski, Johannes Jungwirth et al., https://doi.org/10.1016/j.eclinm.2022.101809, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/s41598-017-13282-7","kind":"article","title":"Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms","authors":["Carhart-Harris RL","Roseman L","Bolstridge M","Demetriou L","Pannekoek JN","Wall MB","Tanner M","Kaelen M","McGonigle J","Murphy K","Leech R","Curran HV","Nutt DJ"],"author_count":13,"year":2017,"published":"2017-10-13","venue":"Scientific reports","cited_by":415,"doi":"10.1038/s41598-017-13282-7","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41598-017-13282-7","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41598-017-13282-7","updated":null,"pmid":"29030624","pmcid":"PMC5640601","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5640601/pdf","abstract":"Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other 'psychedelics' yet were related to clinical outcomes. A 'reset' therapeutic mechanism is proposed.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms\" by Carhart-Harris RL, Roseman L, Bolstridge M et al., https://doi.org/10.1038/s41598-017-13282-7, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/s41586-024-07624-5","kind":"article","title":"Psilocybin desynchronizes the human brain","authors":["Siegel JS","Subramanian S","Perry D","Kay BP","Gordon EM","Laumann TO","Reneau TR","Metcalf NV","Chacko RV","Gratton C","Horan C","Krimmel SR","Shimony JS","Schweiger JA","Wong DF","Bender DA","Scheidter KM","Whiting FI","Padawer-Curry JA","Shinohara RT","Chen Y","Moser J","Yacoub E","Nelson SM","Vizioli L"],"author_count":33,"year":2024,"published":"2024-07-17","venue":"Nature","cited_by":236,"doi":"10.1038/s41586-024-07624-5","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41586-024-07624-5","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41586-024-07624-5","updated":null,"pmid":"39020167","pmcid":"PMC11291293","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC11291293/pdf","abstract":"A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials 1-4 . In animal models, psilocybin induces neuroplasticity in cortex and hippocampus 5-8 . It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Psilocybin desynchronizes the human brain\" by Siegel JS, Subramanian S, Perry D et al., https://doi.org/10.1038/s41586-024-07624-5, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1177/0269881119897615","kind":"article","title":"Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer","authors":["Gabrielle Agin-Liebes","Tara C. Malone","Matthew M. Yalch","Sarah E. Mennenga","Katherine Ponte","Jeffrey R. Guss","Anthony P. Bossis","Jim Grigsby","Stacy M. 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