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Research papers on Psilocybin-assisted therapy for depression

Recent and highly-cited academic work on psilocybin-assisted therapy for depression, gathered from Semantic Scholar, CrossRef and OpenAlex.

1. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

   Robin Carhart‐Harris, Robert Leech, Peter J. Hellyer, et al. · 2014 · Frontiers in Human Neuroscience · 1,308 citations

   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

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2. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder

   Alan K. Davis, Frederick S. Barrett, Darrick G. May, et al. · 2020 · JAMA Psychiatry · 1,299 citations

   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 diagno

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3. REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

   Robin Carhart‐Harris, Karl Friston · 2019 · Pharmacological Reviews · 1,205 citations

   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 wor

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4. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression

   Guy M. Goodwin, Scott T. Aaronson, Oscar Alvarez, et al. · 2022 · New England Journal of Medicine · 1,134 citations

   BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total sco

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5. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

   Robin Carhart‐Harris, Mark Bolstridge, Camilla Day, et al. · 2017 · Psychopharmacology · 990 citations

   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, m

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6. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

   Fernanda Palhano-Fontes, Dayanna Barreto, Heloisa Onias, et al. · 2018 · Psychological Medicine · 838 citations

   BACKGROUND: Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. METHODS: To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. RESULTS: We observed significant antidepressant effects of ayahuasca when compare

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7. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

   Leor Roseman, David Nutt, Robin Carhart‐Harris · 2018 · Frontiers in Pharmacology · 825 citations

   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 trea

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8. The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

   Robin Carhart‐Harris, Guy M. Goodwin · 2017 · Neuropsychopharmacology · 700 citations

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9. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder

   Michael P. Bogenschutz, Stephen Ross, Snehal Bhatt, et al. · 2022 · JAMA Psychiatry · 692 citations

   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 assesse

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10. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms

    Robin Carhart‐Harris, Leor Roseman, Mark Bolstridge, et al. · 2017 · Scientific Reports · 602 citations

    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

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11. Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression

    Roberta Murphy, Hannes Kettner, Rick Zeifman, et al. · 2022 · Frontiers in Pharmacology · 241 citations

    Background:Across psychotherapeutic frameworks, the strength of the therapeutic alliance has been found to correlate with treatment outcomes; however, its role has never been formally assessed in a trial of psychedelic-assisted therapy. We aimed to investigate the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes. Methods:This 2-arm double-blind randomized controlled trial compared escitalopram with psychedelic-assisted therapy for moderate-severe depressive disorder (N= 59). This analysis focused on the psilocybin condition (n= 30), who received two oral doses of 25 mg psilocybin, 3-weeks apart, with psychological

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12. A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy

    Jason B. Luoma, Christina Chwyl, Geoff J. Bathje, et al. · 2020 · Journal of Psychoactive Drugs · 209 citations

    After a two-decade hiatus in which research on psychedelics was essentially halted, placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have begun to be published. We identified nine randomized, placebo-controlled clinical trials of psychedelic-assisted therapy published since 1994. Studies examined psilocybin, LSD (lysergic acid diethylamide), ayahuasca (which contains a combination of N,N-dimethyltryptamine and harmala monoamine oxidase inhibitor alkaloids), and MDMA (3,4-methylenedioxymethamphetamine). We compared the standardized mean difference between the experimental and placebo control group at the primary endpoint. Results indicated a sign

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13. Testing an App-Assisted Treatment for Suicide Prevention in a Randomized Controlled Trial: Effects on Suicide Risk and Depression

    Mia S. O'Toole, Mikkel B. Arendt, Christian M. Pedersen · 2019 · Behavior Therapy · 62 citations

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14. Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial

    Jordan Sloshower, Richard J. Zeifman, Jeffrey Guss, et al. · 2024 · Scientific Reports · 57 citations

    Abstract Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/k

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15. Psilocybin for depression: Considerations for clinical trial design

    Kelley C. O’Donnell, Sarah E. Mennenga, Michael P. Bogenschutz · 2019 · Journal of Psychedelic Studies · 13 citations

    Background and aims Given the enormous global burden of depressive illness, there is an urgent need to develop novel and more effective treatments for major depressive disorder (MDD). Recent findings have suggested that psychedelic drugs may have a role in the treatment of depressive symptoms, and a number of groups are in the process of developing protocols to study this question systematically. Given the subjective quality of both the psychedelic experience and depressive symptomatology, great care must be taken when designing a protocol to study the clinical efficacy of psychedelic drugs. This study will discuss many factors to consider when designing a clinical trial

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16. Evolving Guidelines for the Use of Touch During a Clinical Trial of Group Psilocybin-Assisted Therapy

    Anthony Back, Susanna Myers, John Guy, et al. · 2024 · Psychedelic Medicine · 7 citations

    For a new clinical trial testing a group retreat-based format of psilocybin-assisted therapy, our research team created an initial set of practice guidelines that aimed to describe facilitator use of touch in a way that is ethical, supportive, and minimizes harm. In our first three retreats, however, we had two unexpected experiences with touch that led us to iterate our initial guidelines into a new version of guidelines. In this Technical Report, we describe our evolving guidelines specifying acceptable practices for facilitator use of touch to ensure a safe, supportive, and therapeutic participant experience. Our primary goal with these guidelines is to create a haptic experience during t

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17. Psilocybin-Assisted Therapy May Enhance Conservation Values in Patients with Alcohol Use Disorder

    Noah D. Gold, Broc A. Pagni, Petros D. Petridis, et al. · 2025 · Psychedelic Medicine · 4 citations

    Background: Psilocybin can produce long-term changes in personality, personal values, and behavior. Although psilocybin-assisted therapy (PAT) is being actively studied for various psychiatric conditions, its effects on personal values in patients with alcohol use disorder (AUD) remain unexplored. This study examined the effects of PAT on personal values in patients with AUD and assessed relationships between value changes, acute psilocybin experiences, and drinking outcomes. Methods: In a phase II clinical trial (NCT02061293), 93 participants with AUD

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18. Low-income group psilocybin assisted therapy for depression: An Oregon feasibility study

    Matthew Hicks, Olivia Hicks, Ryan Bradley, et al. · 2026 · Journal of Psychedelic Studies · 2 citations

    Abstract Background and aims Despite growing popularity and increasing legal access, psychedelic therapy remains financially inaccessible to many. This study was designed to test the feasibility of conducting group psilocybin therapy in low-income adults with depression in Oregon's regulated psilocybin program. Methods An open label, uncontrolled design was used. After a medical screening visit, participants were enrolled in cohorts of six. Each cohort participated in two 90-min preparation sessions conducted online followed by two ps

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19. Hormonal Influences on Psilocybin Responsivity Across the Female Lifespan: Toward Personalized Psychedelic-Assisted Therapy

    Faith Ekoh, Shanice Rerrie, James Angud, et al. · 2025 · Psychoactives · 2 citations

    Today’s research highlights the therapeutic potential of the hallucinogen psilocybin in the treatment of pathologies associated with mood, cognitive, and affective dysregulation. These domains of function are regulated by the serotonergic system, which can be influenced by sex hormones, like estrogen and testosterone, and psychedelic compounds including psilocybin. Current evidence supports a higher prevalence of affective disorders in females, and a growing awareness of sex-based differences in response to drug therapy. Estrogen’s influence on serotonin physiology is an aspect that must be accounted for when planning a treatment regimen that includes a psychoactive drug such as psilocybin.

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20. Reporting practices in psilocybin-assisted therapy trials for depression: A descriptive review and temporal overview

    Nils Hörnqvist · 2026 · Journal of Psychedelic Studies

    Abstract Background Research on psilocybin's antidepressant effects has been investigated rigorously over the last 20 years. Psilocybin has been used in both major depressive disorder (MDD) and treatment resistant depression (TRD) cohort with promising results. Aims The aim of this review was to summarize the reporting practices used in psilocybin-assisted therapy (PAT) trials for MDD and TRD. By comparing completed and ongoing PAT, a temporal summary of how reporting practices are projected to change was also investigated.

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21. PSILOCYBIN IN PSYCHIATRIC PRACTICE AND PSYCHEDELIC-ASSISTED THERAPY FOR TREATMENT-RESISTANT DEPRESSION

    Łukasz Deska, Cezary Kosmecki, Dawid Głaz, et al. · 2026 · International Journal of Innovative Technologies in Social Science

    This manuscript comprehensively reviews psilocybin-assisted therapy for major depressive disorder and treatment-resistant depression. It aims to synthesize current understanding regarding its mechanisms, efficacy, safety, costs, and accessibility, comparing it with conventional antidepressant and ketamine treatments. The methodology involved a narrative synthesis of academic literature, drawing from systematic reviews, meta-analyses, and clinical trials identified through targeted database searches. Key findings indicate that psilocybin therapy demonstrates rapid, robust, and sustained antidepressant effects, with high response and remission rates, often after one or two sessions. Its safet

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