medRxiv : the preprint server for health sciences
July 14, 2026
Ali J Zarrabi, Tanja Mletzko, George H. Grant et al.
Demoralization, a syndrome of helplessness, hopelessness, and loss of meaning and chronic pain are common sources of distress in early palliative care. Psilocybin-assisted therapy (PAT) is an emerging intervention with preliminary data suggesting improvements in pain and demoralization. To date, PAT has not been studied among people living with both demoralization and chronic pain nor has it...
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
correction
Corrigendum to "The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression" [Journal of Affective Disorders, Volume 372 (2025), Pages 523-532].
The Journal of Clinical Psychiatry
March 3, 2025
Guy M. Goodwin, Ania Nowakowska, Merve Atli et al.
14 citations
Background: The largest randomized study of psilocybin to date demonstrated the efficacy of COMP360 25 mg (Compass Pathways' investigational proprietary pharmaceutical-grade synthesized psilocybin formulation) in participants with treatment-resistant depression (COMP 001), compared with 10 mg and 1 mg doses. Here, we report findings from COMP 004, a 52-week observational follow-up of patients...
Journal of Affective Disorders
March 1, 2025
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
35 citations
To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression. For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with...
BMC Psychiatry
February 28, 2025
John Perna, Justin Trop, Roman Palitsky et al.
15 citations
This case highlights the tensions between legal and underground psychedelic use within psychedelic therapy training programs, psychiatry and neo-shamanism, and the use of psychiatric interventions (i.e., ECT) and energy medicine to address prolonged adverse effects from psychedelics. Clinicians should be aware of these potential conflicts between psychiatric conceptualizations of PAEs and...
Brain Sciences
February 6, 2025
Michael J Lucido, Boadie W Dunlop
15 citations
Background/Objectives: Non-response to initial treatment options for major depressive disorder (MDD) is a common clinical challenge with profound deleterious impacts for affected patients. Few treatments have received regulatory approval for treatment-resistant depression (TRD). Methods: A systematic search of United States and European Union clinical trials registries was conducted to identify...
Contemporary clinical trials communications
February 1, 2025
Jessica L Maples-Keller, Boadie W Dunlop, Barbara O Rothbaum
5 citations
This article describes the rationale and the specific methods for an open label pilot trial of 100 mg MDMA in combination with massed exposure therapy for PTSD, a treatment which involves daily exposure therapy sessions for two weeks which has found to be effective. We review the need for novel PTSD treatments and the existing research on MDMA-assisted therapy, and then describe the rationale...
Psychotherapy
January 13, 2025
Roman Palitsky, Jessica L Maples-Keller, Caroline Peacock et al.
13 citations
Psilocybin-assisted therapy (PAT) is an experimental treatment with transformative promise. Developing standards for PAT psychotherapy protocols is a priority, but psychotherapeutic protocol components of PAT have been subjected to little rigorous research. This study was designed to assess protocol components in a trial of PAT. The Enhanced Critical Incident Technique (E-CIT) was used to...
Am J Bioeth
January 13, 2025
Keenan Davis, Roman Palitsky, Boadie W Dunlop et al.
3 citations
In their article “Psychedelic Medicine Exceptionalism,” Cohen and Marks (2025) aim to chart a middle course between two extreme positions—the Scylla and Charybdis of psychedelic “exceptionalism” an...
Psychedelics.
December 17, 2024
Zachary Bosshardt, Jessica L Maples-Keller, Deanna M Kaplan et al.
Social attitudes, policy, and perceptions of psychedelics are currently undergoing considerable change. Growing public salience of psychedelics has been accompanied by the emergence of conferences focused on psychedelic education and dialogue. Attendees at such events compose an important group of stakeholders in psychedelic science and practice; their views of psychedelics can be valuable for...
International review of psychiatry (Abingdon, England)
December 1, 2024
Roman Palitsky, Nicholas K. Canby, Nicholas T. van Dam et al.
6 citations
Psychedelics have shown early evidence for a range of benefits and low harm profiles in extant research. However, adverse effects (AEs) research in psychedelics has been limited, leading to underspecified AE profiles, inconsistent measurement, and potential undercounting of AEs. The development of safe, effective psychedelic therapies and treatments for AEs when they occur requires a thorough...
Journal of Psychoactive Drugs
October 23, 2024
Jessica L Maples-Keller, Courtland S Hyatt, Nathaniel L Phillips et al.
2 citations
3,4-methylenedioxymethamphetamine (MDMA) assisted therapy has been shown to be a safe and effective treatment for PTSD and emerging research suggests a change in personality traits may be a factor in treatment response. Most prior research on MDMA and personality has focused on cross-sectional comparisons of MDMA users and non-users; as such, well-controlled research assessing personality and...
Journal of Psychopharmacology
July 31, 2024
Roman Palitsky, Deanna M Kaplan, John Perna et al.
32 citations
Objective: Despite considerable research examining the efficacy of psychedelic-assisted therapies (PATs) for treating psychiatric disorders, assessment of adverse events (AEs) in PAT research has lagged. Current AE reporting standards in PAT trials are poorly calibrated to features of PAT that distinguish it from other treatments, leaving many potential AEs unassessed. Methods: A...
PLoS One
January 2, 2024
Caroline Peacock, Erin Brauer, Ali John Zarrabi et al.
27 citations
Background Psychedelic-assisted therapies hold early promise for treating multiple psychiatric conditions. However, absent standards for the care, teams providing psychedelic-assisted therapy pose a major roadblock to safe administration. Psychedelics often produce spiritually and existentially meaningful experiences, and spiritual health practitioners have been involved in administering...
JAMA
August 31, 2023
Charles L. Raison, Gerard Sanacora, Joshua Woolley et al.
493 citations
Importance Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were...
Psychopharmacology
August 22, 2023
Robert F. Dougherty, Patrick Clarke, Merve Atli et al.
21 citations
Abstract Rationale Therapeutic administration of psychedelics has shown significant potential in historical accounts and recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways’ proprietary synthetic formulation of psilocybin, in participants with...
JAMA Psychiatry
July 1, 2023
Roman Palitsky, Deanna M Kaplan, Caroline Peacock et al.
86 citations
Mounting evidence supports the role of spiritual, existential, religious, and theological components in mediating psychedelic-assisted therapy, yet integration of these elements into the clinical setting is lagging. Although psychedelic-assisted therapy commonly produces spiritually, existentially, religiously, or theologically relevant experiences for patients, these have not been...
Journal of Affective Disorders
February 3, 2023
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
168 citations
Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.
The New England journal of medicine
November 3, 2022
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
Psilocybin is being studied for use in treatment-resistant depression. 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...
Journal of Psychopharmacology
February 15, 2022
Jessica L Maples-Keller, Seth D. Norrholm, Mark Burton et al.
53 citations
Background: Fear conditioning and extinction are well-characterized cross-species models of fear-related posttraumatic stress disorder (PTSD) symptoms, and recent animal data suggest that 3,4-methylenedioxymethamphetamine (MDMA) enhances fear extinction retention. Aims: This study investigated the effect of MDMA on fear learning, extinction training, and retention in healthy humans. Methods:...
Psychopharmacology
July 24, 2017
Matthew B Young, Seth D. Norrholm, Lara M. Khoury et al.
103 citations
We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.