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Benjamin Kelmendi

Yale University, National Center for PTSD

28 papers in the library · 1,131 citations · publishing 2016-2026

Papers

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Surrender, disidentification, and reappraisal: a qualitative comparison of psilocybin responders and non-responders in treatment-resistant OCD

Frontiers in Psychiatry September 1, 2026 Gabrielle Agin-Liebes, Sarah Shnayder, Geena Fram et al.

Introduction Psilocybin treatment has shown promise for treatment-resistant obsessive-compulsive disorder (OCD), yet clinical response is variable. Little is known about the subjective experiences associated with divergent outcomes or the psychological processes differentiating responders from non-responders. Materials and methods A qualitative case comparison was conducted using...

α2-Adrenergic receptor modulates 5-HT2A-mediated behavioral effects of MDMA and psilocybin in mice.

Mol Psychiatry July 7, 2026 Axel F. Rosado, Abigail L. Yu, Jen-Hau Yang et al.

Classic serotonergic psychedelics such as psilocybin act as agonists at cortical serotonin (5-HT) 2A receptors (5-HT 2A R), inducing psychedelic effects in humans and head-twitch responses (HTRs) in rodents. Another class of psychedelic drugs called entactogens, exemplified by MDMA, function primarily as monoamine releasers and typically evoke minimal HTR despite causing serotonin release. The...

Efficacy and Safety of the Neuroplastogen TSND-201 for the Treatment of PTSD: A Randomized Clinical Trial.

JAMA Psychiatry May 1, 2026 Amanda Jones, Jennifer Warner-Schmidt, Hannah Kwak et al. 6 citations

The phase 2 data presented here support the development of TSND-201 for posttraumatic stress disorder (PTSD), a disorder for which there is a significant unmet need for rapid-acting and effective treatments. TSND-201 (methylone) is a highly selective, rapid-acting neuroplastogen that releases serotonin, norepinephrine, and dopamine without direct activity at 5-hydroxytryptamine (5-HT) 2A...

Mystical but Not Challenging Experiences Predict Symptom Improvement After Psilocybin for Treatment-Resistant OCD

February 11, 2026 Sarah Shnayder, Gabrielle Agin-Liebes, Troy Hubert et al. preprint

Background: Psilocybin treatment has shown promise across a range of psychiatric conditions. Mystical-type experiences during dosing sessions have been shown to predict the clinical effects of psilocybin treatment in depression, anxiety, and addiction. However, no studies have examined whether acute subjective experiences predict treatment response in obsessive-compulsive disorder (OCD)....

Psilocybin for Treatment-Resistant OCD: A Randomized Controlled Trial

January 15, 2026 Benjamin Kelmendi, Thomas G. Adams, Terence H. W. Ching et al. preprint

Background: Obsessive-compulsive disorder (OCD) affects 2-3% of the population worldwide. 40-60% of patients do not respond to first-line interventions. We evaluated the efficacy and safety of a single dose of psilocybin in patients with treatment-resistant OCD.Methods: In this phase 2, randomized, double-blind trial, we randomly assigned 28 adults with treatment-resistant OCD to receive a...

A primer for culturally attuned psychedelic clinical trials

Journal of Psychedelic Studies May 15, 2025 Terence H. W. Ching, Benjamin Kelmendi 4 citations

AbstractBackgroundThere is a need to systemically diversify psychedelic clinical trials, considering the growing interest in in the therapeutic potential of psychedelics within Black, Indigenous, and Peoples of Color (BIPOC) and queer communities. Doing so contributes to a more inclusive foundation of evidence-based research and addresses ethical considerations surrounding anticipated demand...

A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research

Psychedelic Medicine January 20, 2025 Marianna Graziosi, Gabrielle Agin-Liebes, Mary P Cosimano et al. 9 citations

Introduction: Serotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for...

Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic

JAMA Network Open December 5, 2024 Anthony L. Back, Timara K Freeman-Young, Ladybird Morgan et al. 37 citations

Importance The psychological morbidity experienced by physicians, advanced practice practitioners (APPs), and nurses from working during the COVID-19 pandemic includes burnout, depression, and posttraumatic stress disorder (PTSD). Objective To investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in US clinicians who developed these symptoms from...

Novel Pharmacologic and Other Somatic Treatment Approaches for Posttraumatic Stress Disorder in Adults: State of the Evidence.

The American journal of psychiatry December 1, 2024 Lauren M. Sippel, Jessica L. Hamblen, Benjamin Kelmendi et al. 11 citations

Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. The most commonly recommended first-line treatments for PTSD among adults are individual trauma-focused psychotherapies. Other evidence-based treatments include specific antidepressant medications and non-trauma-focused psychotherapies. Despite the...

Psychedelic medicine in psychiatry residency training: a survey of psychiatric residency program directors.

Int Rev Psychiatry September 11, 2024 Mary E. Yaden, Terence H. W. Ching, Noam Goldway et al. 2 citations

OBJECTIVE: The growth of psychedelic medicine creates new challenges in psychiatric education as physicians may soon be responsible for prescribing a number of psychedelic interventions. Despite this growing need for educated providers, very little is known about the training psychiatry residents receive in psychedelic medicine. We conducted a survey to determine the current educational...

Mechanisms of therapeutic change after psychedelic treatment in OCD.

Psychiatry Research June 1, 2024 Gayle Maloney, Terence H. W. Ching, Stephen A. Kichuk et al. 3 citations

Novel treatments are required for the 30-50% of individuals with obsessive-compulsive disorder (OCD) who remain resistant to first-line pharmacological and psychotherapeutic treatments. Recent pilot data suggest benefit from psilocybin-assisted psychotherapy (PAP) and from imagery rescripting (ImRs). We explore psychological mechanisms of change underpinning both interventions that appear to...

Corrigendum: Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings

Frontiers in Psychiatry February 16, 2024 Terence H. W. Ching, Lucia Amoroso, Calvin Bohner et al. correction

[This corrects the article DOI: 10.3389/fpsyt.2023.1278823.].

Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

Frontiers in Neuroscience February 7, 2024 Jennifer Warner-Schmidt, Martin Stogniew, Blake Mandell et al. 6 citations

BackgroundPost-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Available pharmacotherapies are limited, take weeks to show modest benefit and remain ineffective for up to 40% of patients. Methylone is currently in clinical development for the treatment of PTSD. Preclinical studies show rapid, robust and...

Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings

Frontiers in Psychiatry January 9, 2024 Terence H. W. Ching, Lucia Amoroso, Calvin Bohner et al. 9 citations

Background To date, few randomized controlled trials of psilocybin with non-directive support exist for obsessive-compulsive disorder (OCD). Results and participant feedback from an interim analysis of an ongoing single-dose trial (NCT03356483) converged on the possibility of administering a higher fixed dose and/or more doses of psilocybin in future trials for presumably greater benefits....

Single-Dose Psilocybin Treatment for Major Depressive Disorder

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...

Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive–compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial

Frontiers in Psychiatry April 25, 2023 Rachael Grazioplene, Calvin Bohner, Giuliana DePalmer et al. 27 citations

Background Psilocybin may help treat obsessive–compulsive disorder (OCD). To date, only one open-label study of psilocybin for OCD exists, necessitating further investigation with a randomized controlled design. The neural correlates of psilocybin’s effects on OCD have also not been studied. Objectives This first-of-its-kind trial aims to evaluate the feasibility, safety, and tolerability of...

Yale Program for Psychedelic Science (YPPS) Manual for Psilocybin Combined with Non-Directive Support in the Treatment of OCD

March 17, 2023 Terence H. W. Ching, Rachael Grazioplene, Christopher Pittenger et al. 6 citations preprint

The Yale Program for Psychedelic Science (YPPS) supports a multi-disciplinary research community dedicated to investigating the effects of psychedelic substances on brain function, cognition, and behavior, including their therapeutic potential in treating neuropsychiatric conditions. In support of this mission, YPPS is testing the safety and efficacy of psilocybin, administered in conjunction...

Pharmacological effects of methylone and MDMA in humans

Frontiers in Pharmacology February 17, 2023 Lourdes Poyatos, Clara Pérez‐mañá, Olga Hladun et al. 26 citations

Methylone is one of the most common synthetic cathinones popularized as a substitute for 3,4-methylenedioxymethamphetamine (MDMA, midomafetamine) owing to its similar effects among users. Both psychostimulants exhibit similar chemistry (i.e., methylone is a β-keto analog of MDMA) and mechanisms of action. Currently, the pharmacology of methylone remains scarcely explored in humans. Herein, we...

Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD

Frontiers in Psychiatry February 6, 2023 Candace R. Lewis, Joseph Tafur, Sophie Spencer et al. 29 citations

BackgroundPrevious research has demonstrated that epigenetic changes in specific hypothalamic-pituitary-adrenal (HPA) genes may predict successful psychotherapy in post-traumatic stress disorder (PTSD). A recent Phase 3 clinical trial reported high efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for treating patients with severe PTSD compared to a therapy with placebo...

Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity

Frontiers in Psychiatry January 10, 2023 Jennifer Warner-Schmidt, Christopher Pittenger, Martin Stogniew et al. 11 citations

Introduction Selective serotonin reuptake inhibitor (SSRI) antidepressants represent first-line pharmacological treatment for a variety of neuropsychiatric illnesses, including major depressive disorder (MDD), anxiety, and post-traumatic stress disorder (PTSD), which show high rates of comorbidity. SSRIs have a delayed onset of action. Most patients do not show significant effects until 4–8...

Single-dose psilocybin for treatment-resistant obsessive-compulsive disorder: A case report

Heliyon December 1, 2022 Benjamin Kelmendi, Giuliana DePalmer, Gayle Maloney et al. 34 citations

Classic psychedelics, such as psilocybin, act on the brain's serotonin system and produce striking psychological effects. Early work in the 1950s and 1960s and more recent controlled studies suggest benefit from psychedelic treatment in a number of conditions. A few case reports in recreational users and a single experimental study suggest benefit in patients with obsessive-compulsive disorder...

Yale Program for Psychedelic Science (YPPS) Manual for Psilocybin-OCD Session Monitors for Protocol HIC: 2000020355

October 5, 2022 Terence H. W. Ching, Stephen A. Kichuk, Giuliana DePalmer et al. 5 citations preprint

The Yale Program for Psychedelic Science (YPPS) is testing the safety and efficacy of psilocybin, administered in conjunction with non-directive psychological support, as a treatment for certain neurological and psychiatric conditions. The study, HIC: 200020355 (Neural correlates of the effects of psilocybin in obsessive-compulsive disorder: A double-blind, placebo-controlled study), will...

Psychedelics.

Curr Biol 2022 Benjamin Kelmendi, Alfred P. Kaye, Christopher Pittenger et al. 115 citations

Psychedelics are compounds that alter consciousness by acting on serotonin receptors in the brain. The term 'psychedelic', from the Greek for mind manifesting, refers to the drugs' subjective effects and was first proposed by Humphry Osmond in 1956. Other terms have been used to emphasize different aspects of the psychological experiences produced by various related compounds, including...