Psilocin is a psychedelic indole alkaloid and one of the major human metabolites of its phosphorylated precursor, psilocybin. Psilocin binds to the serotonin receptor, 5-HT2A, and dose-dependently induces hallucinogenic effects stronger than psilocybin. As a result, psilocin has been a drug of interest in the analytical toxicology community for years. In viv...
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...
Importance: Cocaine use disorder is a serious public health problem and no medications have been proven effective for its treatment. Objective: To evaluate psilocybin in the treatment of cocaine use disorder. It was hypothesized that psilocybin, compared with placebo, would yield a higher percentage of cocaine abstinent days, a greater likelihood of complete...
Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants...
Abstract Introduction Psychedelic use and interest in its therapeutic potential are rapidly increasing; yet its relationship with insomnia remains poorly understood. This study aims to estimate differences in insomnia severity by type of psychedelic consumed among a cohort of 18-to-35-year olds. Methods Data are from the Herbal Heart Study - Sleep Ancillary ...
Objectives: For English, the validated part of Psychedelic Experience Scale (PES48) is a four-factor structure called the Mystical Experience Questionnaire (MEQ30). The other validated part of the PES48 consists of four more factors: two more mystical factors (paradoxicality and connectedness, which together with the MEQ30 form the MEQ40), and two more non-m...
Prolonged grief disorder (PGD) affects approximately 10% of bereaved individuals and is now formally recognized in both the DSM-5-TR and ICD-11. Despite its prevalence, PGD often responds poorly to traditional therapeutic approaches. This manuscript outlines the protocol for an early-stage open-label feasibility trial investigating the use of psilocybin, a p...
Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses and protein synthesis. However, the exact molecular and cellular changes induced by psilocybin in the human brain are not known. Here, we treated h...
Background/Objectives: Psilocybin has re-emerged as a promising intervention for neuropsychiatric disorders including major depressive disorder, treatment-resistant depression, anxiety associated with life-threatening illness, obsessive compulsive disorder, and substance use disorders. However, conventional randomized controlled trials (RCTs)-the current gol...
Depression and psychological distress are highly prevalent among patients with cancer and are associated with impaired quality of life, reduced treatment adherence, and poorer clinical outcomes. Standard pharmacological and psychosocial interventions often demonstrate limited efficacy or delayed onset of action in oncological and palliative settings. Psilocy...
Importance: Psilocybin shows promise in treating depression, although limitations of previous research warrant further research. Objective: To investigate the efficacy and safety of oral psilocybin, 25 mg, with adjunct psychotherapy in treatment-resistant depression (TRD). Design, Setting, and Participants: This was a 2-center, triple-blinded (investigator, ...
BACKGROUND AND AIMS: There has been a resurgence of interest in using psilocybin to treat various mental health conditions. Although some adults in the United States (US) are using psilocybin, little is known about the epidemiology of its use, especially for microdosing (i.e., taking a fraction of a regular dose). This study aimed to present nationally repre...
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...
PcncAAAD is a noncanonical fungal aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-binding sites. Unlike its mammalian and plant counterparts, PcncAAAD is activated by calcium, although the exact activation mechanism remains unclear. Here, we establish an in silico RMSD-based evaluation model throu...
