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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. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder

   Alan K. Davis, Frederick Streeter Barrett, Darrick G. May, et al. · 2020 · JAMA Psychiatry · 1,292 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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2. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

   Leor Roseman, David Nutt, Robin Lester Carhart-Harris · 2018 · Frontiers in Pharmacology · 805 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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3. Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression

   Roberta Murphy, Hannes Kettner, Richard J. Zeifman, et al. · 2022 · Frontiers in Pharmacology · 247 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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4. 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 · 212 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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5. The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder

   Adam W. Levin, R. Lancelotta, N. Sepeda, et al. · 2024 · PLOS ONE · 80 citations

   We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive disorder in adults (N = 24), participants were randomized to an immediate (N = 13) or delayed (N = 11) condition with two oral doses of psilocybin (20mg/70kg and 30mg/70kg). Ratings of therapeutic alliance significantly increased from the final preparation session to one-week post-intervention (p = .03, d = .43). A stronger total alliance at the final

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

   Jordan Sloshower, R. Zeifman, Jeffrey R. Guss, et al. · 2024 · Scientific Reports · 65 citations

   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/kg) (n = 15) 4 weeks later.

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7. 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 · 63 citations

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8. Psilocybin-Assisted Compassion Focused Therapy for Depression

   Wendy T. M. Pots, Farid Chakhssi · 2022 · Frontiers in Psychology · 33 citations

   Psilocybin-assisted psychotherapy, i.e., psilocybin treatment with psychological support, has demonstrated the efficacy of psilocybin to reduce depressive symptoms. However, in clinical trials, the structure of psilocybin-assisted psychotherapy is primarily based on preparation, navigation (support during dosing sessions), and integration. For psychotherapeutic guidance, the application of this structure is favored over the usage of theoretical models. The applied psychotherapeutic models may be of critical importance if the effects are augmented due to the psychologically insightful experiences during the navigation and integration sessions. One of the important next steps is to provide the

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9. Psychedelics assisting therapy, or therapy assisting psychedelics? The importance of psychotherapy in psychedelic-assisted therapy

   Joseph A. Zamaria, Gisele Fernandes‐Osterhold, Jonathan Shedler, et al. · 2025 · Frontiers in Psychology · 28 citations

   There is notable controversy about the role of psychotherapy in clinical trials of psychedelic-assisted therapy (PAT). This heated and perpetually evolving debate informs questions such as how much therapy should accompany a psychedelic intervention (Marseille et al., 2022), what type of therapy most effectively complements psychedelic administration (Cavarra et al., 2022;Yaden et al., 2022), and even whether psychotherapy should always be included (Goodwin et al., 2023;Earleywine et al., 2024;Schenberg, 2024). Recent events, namely the rejection by the Food and Drug Administration (FDA) of Lykos Therapeutics' application to approve MDMA-assisted therapy (MDMA-AT) as a treatment for PTSD, ha

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10. Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial.

    B. Pagni, R. Zeifman, S. Mennenga, et al. · 2025 · The American journal of psychiatry · 26 citations

    OBJECTIVE Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking. METHODS Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psych

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11. Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial.

    F. Müller, H. Zaczek, Anna M. Becker, et al. · 2025 · Med · 25 citations

    BACKGROUND This trial aimed to assess the efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with moderate-to-severe major depressive disorder. METHODS This was a randomized, parallel, double-blind, low-dose controlled trial (Clinicaltrials.gov: NCT03866252). Patients were randomly assigned in a 1:1 ratio to receive supportive psychotherapy and either 100 μg + 200 μg LSD or 25 μg + 25 μg LSD in two dosing sessions. The primary endpoints were the changes in scores on the Inventory of Depressive Symptomatology, in the Clinician-Rated (IDS-C) version (assessed by the treating therapist) and the Self-Rated (IDS-SR) version, from baseline to 2 weeks after the second admin

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12. In the New Era of Psychedelic Assisted Therapy: A Systematic Review of Study Methodology in Randomized Controlled Trials

    Paul S Soliman, Dallece E. Curley, Christy Capone, et al. · 2024 · Psychopharmacology · 20 citations

    Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorders. A notable methodological challenge in psychedelic AT, however, is the complexity of blinding procedures. The lack of efficacious blinding can introduce considerable response bias, reduce internal validity, and compromise participant retention. This systematic review examines design and blinding techniques in RCTs utilizing psychedelic

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13. Psilocybin-assisted psychotherapy for depression and anxiety associated with life threatening illness: A phase 2b randomized controlled trial.

    Margaret Ross, R. Iyer, Martin L. Williams, et al. · 2025 · General hospital psychiatry · 19 citations

    IMPORTANCE Psilocybin-assisted psychotherapy may offer a novel approach to treating depression, anxiety, and existential distress in individuals with life threatening illnesses, where current treatments show limited efficacy. OBJECTIVE To evaluate the efficacy and safety of psilocybin-assisted psychotherapy versus active placebo and psychotherapy in adults with life-threatening illnesses. DESIGN Double-blind, randomized controlled phase 2b trial (RCT) with an open-label extension and 6-month follow-up (January 2020 - October 2023). SETTING Single-site study at a tertiary hospital's palliative care department (St. Vincent's Hospital Melbourne affiliated with the University of Melbourne)

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14. Randomized Controlled Trials of Psilocybin‐Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta‐Analysis

    V. Menon, Parthasarathy Ramamurthy, Sandesh Venu, et al. · 2024 · Acta Psychiatrica Scandinavica · 16 citations

    There is growing interest in the use of psychedelic‐assisted therapy (PAT) for major depressive disorder (MDD), including treatment‐resistant depression. We used randomized controlled trial (RCT) data to compare summary estimates of change in depression ratings with PAT versus comparator treatments in MDD. We also compared response and remission rates, and adverse effects.

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15. Psilocybin-assisted group psychotherapy and mindfulness-based stress reduction for frontline healthcare provider COVID-19-related depression and burnout: A randomized controlled trial

    Benjamin R. Lewis, John Hendrick, Kevin Byrne, et al. · 2025 · PLOS Medicine · 14 citations

    Background Depression and burnout, which are common among healthcare workers, were exacerbated by the COVID-19 pandemic. Mindfulness-Based Stress Reduction (MBSR) and psilocybin have been reported to reduce depressive symptoms, but the efficacy of the combination requires comparison to an active treatment control. We sought to evaluate the safety and preliminary efficacy of psilocybin and MBSR versus MBSR alone for frontline healthcare providers with symptoms of depression and burnout related to the COVID-19 pandemic. We hypothesized that psilocybin would augment the antidepressant effects of MBSR in this population. Methods and findings We conducted a randomized controlled trial that enroll

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16. Psilocybin for depression: Considerations for clinical trial design

    Kelley C. O’Donnell, Sarah E. Mennenga, Michael P. Bogenschutz · 2019 · Journal of Psychedelic Studies · 14 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 of psilocybin for M

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17. Psychedelic-assisted therapy: An overview for the internist

    B. Barnett, Erin E. Mauney, Franklin King · 2025 · Cleveland Clinic Journal of Medicine · 13 citations

    Preliminary evidence suggests that psychedelic-assisted therapy—the enhancement of psychotherapy with psychedelics such as 3,4-methylenedioxymethamphet-amine (MDMA) and psilocybin—may be efficacious for depression, posttraumatic stress disorder, substance use disorders, and other conditions. Therapeutic psychedelic research is advancing steadily, with psilocybin, MDMA, and lysergic acid diethylamide designated breakthrough therapies by the US Food and Drug Administration (FDA). However, in August 2024, the FDA declined to approve a New Drug Application for MDMA and asked its sponsor to conduct another phase 3 trial. Clinicians are urged to prepare for the possible return of psychedelics to m

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18. Psychedelic-Assisted Therapies for Psychosocial Symptoms in Cancer: A Systematic Review and Meta-Analysis

    Haley D. M. Schuman, Chantal Savard, Raèf Mina, et al. · 2025 · Current Oncology · 12 citations

    This systematic review and meta-analysis evaluates (1) the effectiveness of psychedelic-assisted therapy (PAT) using psilocybin and ketamine for psychosocial symptoms in adults with cancer, (2) contextualizes findings with non-randomized and exploratory studies of other psychedelics, and (3) examines the role of therapeutic frameworks in shaping outcomes. We searched PubMed, Cochrane Library, PsycINFO, and EMBASE (2000–2024) for randomized controlled trials (RCTs) and non-randomized studies investigating psychedelic agents in cancer populations. Meta-analyses pooled RCTs of psilocybin or ketamine using random-effects models. Non-randomized studies were synthesized narratively. Risk of bias a

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19. Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial

    Laetitia Vanderijst, Felix Hever, A. Buot, et al. · 2024 · BMC Psychiatry · 11 citations

    A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction. In this doubl

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20. Treating comorbid insomnia in patients enrolled in therapist-assisted transdiagnostic internet-delivered cognitive behaviour therapy for anxiety and depression: A randomized controlled trial

    M. Edmonds, V. Peynenburg, V. Kaldo, et al. · 2024 · Internet Interventions · 9 citations

    Transdiagnostic Internet-delivered cognitive behaviour therapy (ICBT) for patients experiencing anxiety and depression can produce large improvements in symptoms. Comorbid insomnia is common among individuals seeking treatment for anxiety and depression, yet transdiagnostic ICBT rarely targets insomnia and many ICBT patients report that symptoms of insomnia remain after treatment. This trial explored the impact of including a brief intervention for insomnia alongside an existing transdiagnostic ICBT course that included brief weekly therapist assistance. Patients were randomly assigned to receive either the Standard transdiagnostic (n = 75) or a Sleep-Enhanced course (n = 142), which include

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21. Mapping Psilocybin-Assisted Therapies: A Scoping Review

    Ron Shore, Paul Ioudovski, Craig E. Goldie, et al. · 2019 · medRxiv · 8 citations

    Abstract We conducted a scoping review on psilocybin-assisted therapy for addiction, depression, anxiety and post-traumatic stress disorder. Psilocybin is a naturally-occurring tryptophan derivative found in species of mushroom with psycho-active properties. From 2022 records identified by database searching, 40 publications were included in the qualitative synthesis from which we identified 9 clinical trials with a total of 169 participants. Trials used a peak-psychedelic model of therapy, emphasizing inward journey through the use of eyeshades, set musical scores and with medium to high doses of psilocybin. No serious adverse effects were reported; mild adverse effects included transient a

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

    Faith Ekoh, Shanice Rerrie, James Angud, et al. · 2025 · Psychoactives · 4 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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24. 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 received 12 weeks of treatment, including manualized psychotherapy and two 8-h drug administration sessions with either psilocybin ( n = 48)

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