One hundred twenty healthy participants, ages 21 to 70, who experience moderate-to-lower-than-average mental well-being will be evenly randomized into four different study arms, using a 2x2 factorial design. Depending on the study arm, participants will either receive an inactive placebo or up to 25mg psilocybin (oral dose), in one of two set and setting con...
In this single-arm Phase 2 study, the researchers are assessing the feasibility of the group retreat format for clinicians and explores different 'doses' of preparation. A sequential dose-escalation design is used. The study will recruit healthcare clinicians (physicians, nurses, nurse practitioners, physician assistants) aged 25-70 years currently in clinic...
Chronic pain states remain challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin produces a sustained anti-nociceptive effect in chronic neuropathic pain models in male and female mice, mediated primarily by 5-HT2A receptors. Critically, psilocybin significantly potentiates the analgesic efficacy of gabapen...
Introduction: Psilocybin therapy has demonstrated efficacy for cancer-related anxiety and depression, but resource-intensive individual treatment models raise important questions for psychedelic public health about equitable access and scalability. In our prior Phase 1/2 study of group retreat psilocybin therapy for patients with metastatic cancer, we observ...
Psilocybin, chemically known as (4-phosphoryloxy-N, N-dimethyltryptamine, 4-PODMT), is derived from the psychoactive mushroom genus, Psilocybe. Of the four active metabolites, psilocin readily enters systemic circulation. The psychoactive effects of psilocin are thought to arise through partial agonist effects at the 5-HT2A receptor. Psychedelic drugs, inclu...
The primary purpose of this study is to preliminarily estimate the efficacy of psilocybin-facilitated treatment for fibromyalgia. Investigators will assess the impact of psilocybin-facilitated treatment on pain, fatigue, and other fibromyalgia symptoms, in addition to the level of functioning and quality of life. Investigators will also evaluate potential me...
To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), along with putative minor metabolites and several deuterium-labeled derivatives. Psilocybin, psilocin, psilocin-O-glucuronide, and 4-HIAA were assayed for engage...
Detecting psilocybin use is challenging because it rapidly converts to its psychoactive metabolite psilocin, and both compounds are unstable in blood. Bufotenin, a structural isomer of psilocin, may exhibit comparable instability in blood. For reliable detection, we developed and validated an LC-MS/MS method to simultaneously quantify psilocin, bufotenin, an...
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 obsess...
Naturalistic psychedelic use can result in a range of difficulties that impair social, occupational, and other important areas of functioning. Yet, the prevalence, phenomenology, and etiology of these outcomes remain poorly understood. Recent qualitative research has shown that individuals with long-term difficulties after psychedelic use sometimes attribute...
About 30-50% of patients with advanced illness experience depression, anxiety, or decreased sense of purpose and autonomy. Together, these are called psychological distress. Treatment options such as medication and therapy are available; however, they do not always work and can be time-consuming and expensive. We need treatments that work well, quickly, and ...
A key distinction among clinical trials on psilocybin treatments, for example, those targeting depression, has been whether the psilocybin dosing session is combined with bona fide psychotherapy or with what is referred to as “psychological support” (1-3). The most developed model of psychological support is the Compass Psychological Support Model (CPSM; 1)....
OBJECTIVE: Anxiety is common in patients receiving end-of-life care and significantly impacts their quality of life. However, pharmacological management remains challenging due to complex clinical presentations and potential side effects, emphasizing the need for systematically reviewing existing treatments. Here we aim to systematically evaluate the efficac...
Psychotic symptoms are uncommon and non-specific adverse effects of classic (serotonergic) psychedelics such as lysergic acid diethylamide (LSD), psilocybin, and mescaline. They can emerge during the acute phase of psychedelic drug effects, persist into the subacute ("afterglow") period, or, in rare cases, develop into long-term psychotic illness. Across all...
Major depressive disorder (MDD), including treatment-resistant depression (TRD), is a highly prevalent psychiatric disorder. MDD is associated with severe suffering, burden and large economical costs. Although various conventional antidepressant treatments are available, a large portion of depressed people does not or not adequately respond to the first-line...
BACKGROUND AND AIMS: There is an urgent unmet need for novel treatments for methamphetamine (MA) use disorder. We explored the qualitative experiences of people participating in a study of psilocybin-assisted psychotherapy (PAT) to treat MA use disorder. DESIGN AND SETTING: Qualitative study of participants enrolled in a single arm, open-label pilot study of...
Eating disorders (ED) remain challenging to treat, with high dropout and low remission rates in cognitive-behavioral therapy for EDs (CBT-ED). Psilocybin treatment (PT) demonstrates therapeutic potential to enhance CBT-ED by exerting several neurobiological, psychological, and experiential effects (e.g., antidepressant, neuroplasticity, emotional openness) t...
This randomised controlled feasibility trial evaluates the Digital Intervention for Psychedelic Preparation (DIPP), a novel 21-day self-guided program designed to prepare individuals for psychedelic experiences. Forty healthy volunteers will be randomly assigned to either a meditation-based intervention or a music-based control condition. Both groups will fo...
First-hand experience with psychedelics may help clinicians develop skills and knowledge needed to work with the profound changes to conscious awareness occasioned by psychedelics. However, the topic remains contentious and underexplored. In this world-first study, we investigated the utility of psilocybin experiential therapist training in a sample of 14 me...
Serotonergic psychedelics like psilocybin and LSD have shown potential therapeutic benefits for mental health conditions, including depression, PTSD, and addiction. However, research remains limited due to regulatory barriers and a lack of diversity in study populations. Spanish-speaking individuals, despite their significant global and U.S. presence, are un...
