Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia

The primary objective is to evaluate whether a single dose of psilocybin (25 mg), compared to placebo, can restore fronto-striatal reward circuit function and thereby improve anhedonia and emotional blunting in individuals with residual symptoms despite ongoing SSRI or SNRI treatment. This will be assessed using precision functional mapping (PFM), task-based...

Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression (EPIsoDE): 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial.

IntroductionPsilocybin shows promise for treatment-resistant depression (TRD), but long-term data are limited. This study examined the antidepressant effect of one or two psilocybin doses with adjunct psychotherapy in TRD until twelve months.MethodsThis is a naturalistic follow-up of a phase 2b, randomized, active placebo-controlled trial, where participants...

Correction: Catatonia Associated With First-Time Psilocybin Exposure: A Case Report.

[This corrects the article DOI: 10.7759/cureus.106474.].

The Safety and Acceptability of Psilocybin With Support and With Massed Prolonged Exposure Therapy for PTSD

This pilot study will examine the safety, tolerability, acceptability, and efficacy of combination psilocybin + psychotherapy to decrease PTSD symptoms. Participants will be randomized into two different treatment groups, allowing the investigators to directly compare PE augmented with psilocybin and psilocybin-assisted psychotherapy. The Primary objective i...

Environmental and Internal Gating of Memory: ARCH Multiplicative Threshold Framework for Encoding and Retrieval

Memory encoding depends on the joint convergence of substrate readiness, internal drive, environmental input, and a permissive temporal-physiological state. The same logic recurs across vertebrate learning systems: hippocampal-dependent spatial and schema-modulated memory (the Navigia substrate in the Systema Behavorum taxonomy), filial imprinting in the chi...

Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder.

The serotonergic hallucinogen psilocybin has shown potential as a treatment for psychiatric conditions like alcohol use disorder (AUD) and depression in clinical studies. Epigenetic mechanisms, including DNA methylation, are hypothesized to contribute to its lasting therapeutic benefits. In this exploratory study, we present the first methylome-wide analysis...

Mystery shopper assessments of cannabis retailer practices and regulatory compliance in five U.S. states, 2025.

ObjectiveThis study used mystery shoppers to assess cannabis retail practices in 5 US states regulating legal nonmedical cannabis retail.MethodsThis mystery shopper study assessed 130 cannabis retailers in 5 cities (Los Angeles [LA], California; Las Vegas [LV], Nevada; Denver, Colorado; Portland, Oregon; Seattle, Washington) in summer 2025. Researchers recor...

Psilocybin modulates social behaviour in male and female mice in a time-dependent manner.

With the resurgence of psychedelic research and growing evidence of their therapeutic potential, there is an urgent need to understand how these compounds act across biological sexes. Despite widespread interest in their use for conditions marked by social impairments, including depression, anxiety, and anorexia nervosa, the influence of sex as a biological ...

Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms.

Psilocybin is a serotonergic 5-HT2A R agonist that causes psychedelic and anxiolytic effects in human users. To delineate conservation of psilocybin pharmacology, we investigated behavioral effects of psilocybin in planarians ( Dugesia dorotocephala ), the simplest living animal with cephalization that also has a well defined serotonin (5-hydroxytryptamine [...

Overcoming Pharmacokinetic and Peripheral Safety Challenges in Psychedelic Therapies: The Promise of Advanced Drug Delivery Systems.

Classic serotonergic psychedelics-such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT)-hold remarkable promise for treating neuropsychiatric disorders, yet their clinical translation is severely constrained by first-pass metabolism, erratic pharmacokinetics, unsuitable action profiles, and off-target peripheral serotonin eff...

Serotonergic Psychedelics as a Potential Therapeutic Strategy for Anxiety, A Systematic Review

Background and objective: Anxiety disorders are among the most prevalent psychiatric disorders worldwide and affect all age groups. Current pharmacological treatments, such as selective serotonergic reuptake inhibitors (SSRI’s) and benzodiazepines, have limitations in terms of adverse effects and efficacy, which highlights the need for alternative therapies....

Serotonergic Psychedelics as a Potential Therapeutic Strategy for Anxiety, A Systematic Review

Background and objective: Anxiety disorders are among the most prevalent psychiatric disorders worldwide and affect all age groups. Current pharmacological treatments, such as selective serotonergic reuptake inhibitors (SSRI’s) and benzodiazepines, have limitations in terms of adverse effects and efficacy, which highlights the need for alternative therapies....

Psilocybin

Effects of Psilocybin With Psychological Support on Anhedonia in Treatment-resistant Depression: a Randomized Controlled Pilot Trial

The purpose of this study is to evaluate the efficacy of psilocybin on the symptom of anhedonia in individuals with treatment-resistant major depressive disorder.

Group Psilocybin-Assisted Therapy for Post-Traumatic Stress Disorder

This study is a community-informed, pragmatic, open-label, phase 1 clinical trial of group-format psilocybin-assisted therapy (GPAT) for individuals with post-traumatic stress disorder (PTSD). The primary objectives of this phase 1 study are to assess the safety and feasibility of (GPAT) for individuals with (PTSD) and to evaluate preliminary effects on PTSD...

PsiConnect: Multimodal Neuroimaging of Context-Dependent Brain and Behaviour Dynamics under Psilocybin.

PsiConnect is a large-scale neuroimaging study designed to investigate context-dependent neural and subjective effects of psilocybin using multimodal neuroimaging. It combines functional, structural, and diffusion-weighted MRI with EEG to examine brain activity in 62 participants before and after a 19 mg dose of psilocybin. The design includes resting-state ...

Mescaline Alters Cerebellar Function, Global Connectivity, and Frequency-Selective Acoustic Gating: A BOLD fMRI Study in Awake Rats.

Mescaline, a 5-HT2A agonist psychedelic used ceremonially for millennia, lacks neuroimaging characterization due to its Schedule 1 status. Using pharmacological and resting-state fMRI in awake rats, we report mescaline's first comprehensive neurobiological profile. Acutely, mescaline produced cerebellar-selective BOLD suppression, suggesting functional disco...

A Pilot Mechanistic Study of Psilocybin-Assisted Therapy as a Treatment for Depression

Depression is the leading cause of disability worldwide, affecting an estimated 300 million people. Despite available treatments, response rates remain modest, and treatment resistance is common. Novel treatments are needed that act rapidly, produce lasting effects and work differently than existing antidepressants. In clinical trials, psilocybin has shown p...

265 Self-reported rates of psilocybin use in North Florida, 2012 to present

361 Effect of intravenous psilocybin on mechanical hypersensitivity in a rat model of reserpine-induced chronic centralized pain