Interest in psychedelic medicine is increasing, yet psychiatry trainees report limited education in this area. The authors developed a standardized curriculum and evaluated its impact on trainee knowledge and attitudes toward psychedelic medicines. A 6-h psychedelic medicine course was delivered across four psychiatry residency programs in the Northeast United States in 2025-2026. The...
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...
Molecular PsychiatryJuly 7, 2026Axel 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...
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated antidepressant effects in Phase 3 clinical trials, some of its psychedelic effects limit tolerability, necessitating administration in highly supervised clinical settings, and thus motivating development of serotonergic therapeutics that preserve...
Abstract Fear extinction requires dynamic updating of cortical representations, yet the neural mechanisms underlying successful extinction remain poorly understood. Some psychoactive substances induce structural plasticity in medial prefrontal cortex (mPFC), possibly underlying their therapeutic potential. Here we investigated whether MDMA, which enhances fear extinction, induces prefrontal...
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)....
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...
Background: Obsessive-compulsive disorder (OCD) affects 2–3% of the population worldwide, and 40–60% of patients do not respond to first-line treatments. We evaluated the efficacy and safety of a single dose of psilocybin in adults with treatment-resistant OCD.Methods: In this phase 2, randomised, double-blind, placebo-controlled trial at the Connecticut Mental Health Center, Yale University...
Introduction The subjective effects of psilocybin on obsessive-compulsive disorder (OCD) are under-explored. Therefore, we conducted a qualitative study of participant experiences from the first randomized placebo-controlled trial of single-dose psilocybin combined with unstructured and non-directive support for individuals with treatment-refractory OCD. Our research explored how participants...
Despite national efforts to curb the opioid crisis, the clinical and societal challenges continue to grow. FDA-approved medications for opioid use disorder (OUD) are effective but are associated with high rates of treatment discontinuation and relapse. A collection of agents with acute effects on consciousness, collectively (if variably) categorized as 'psychedelics', have emerged as potential...
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...
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...
Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions...
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....
Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions...
Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase...
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...
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...
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...
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...
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 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...
A subanesthetic dose of ketamine causes acute psychotomimetic symptoms and sustained antidepressant effects. In prefrontal cortex, the prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as ketamine act preferentially on GABAergic neurons. However, cortical interneurons are heterogeneous. In particular, somatostatin-expressing (SST)...
The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers...