This project will employ functional brain imaging to study the mechanism and immediate and long-term effects of psilocybin, a serotonin receptor 2A agonist, on cortical and cortico-subcortical brain networks in healthy adults.
Topic Healthy Subjects
Compound Psilocybin
Country United States of America
Visit trial
Status
Not yet recruiting
Results Published
No
Start date
01 July 2021
End date
31 December 2021
Chance of happening
90%
Phase
Phase I
Design
Open
Type
Interventional
Generation
First
Participants
25
Sex
All
Age
18- 40
Therapy
No
Trial Details
Psilocybin shows promise as a safe, transformational therapeutic across several psychiatric conditions. However, little is know about its mechanism of action. This study aims to establish a neuroimaging paradigm for use in future clinical research testing the effectiveness of psilocybin in various clinical applications. In this study, we will assess both acute (during psilocybin exposure) and sustained (one week post-exposure) effects of 5-HT2A receptor agonism on brain circuits using resting state functional connectivity and precision functional mapping (PFM). Using a randomized, controlled crossover study design, a small number of healthy volunteers will receive either psilocybin or methylphenidate (MTP) and will undergo MRI (structural, task, blood flow, extended resting state). After two weeks, participants will return for a second exposure with the alternate of what they received in the first session. This study involves up to five separate imaging sessions. Functional connectivity will be measured using the following PFM approach: 1. Extended functional magnetic resonance imaging (fMRI) image acquisition 2. Aggressive data cleaning 3. Analysis designed to examine functional brain connectivity at the individual level This will allow us to map the effects of 5-HT2A receptor agonism on cortical and cortico-subcortical brain networks at the individual level with precision that is unparalleled in the current literature. This is the first step in developing a precision neuroimaging approach for mechanistic understanding of psilocybin's therapeutic effects. If successful, this pharmacoimaging paradigm will have potential utility across psychiatric conditions, allowing us to better understand whether and how psilocybin might "bend the curve" in treatment course, preventing persistent suffering, disability, and suicide.NCT Number NCT04501653
Sponsors & Collaborators
Washington University School of MedicineLocated in St. Louis Missouri, researchers at the Washington University School of Medicine have conducted a number of studies with psychedelics inlcuding ketamine, psilocybin and nitrous oxide.
Papers
Psilocybin desynchronizes the human brainThis functional mapping study (n=24) examined brain changes in healthy adults before, during, and up to 3 weeks after taking oral psilocybin (25mg) and methylphenidate (Ritalin), with a follow-up 6+ months later. Psilocybin caused over 3-fold greater acute changes in functional networks than Ritalin, with the most significant disruptions observed in the default mode network (DMN), linked to our sense of self. While a perceptual task reduced these changes, suggesting a way to ground individuals during psychedelic therapy, the acute effects of psilocybin were consistent with distortions of space-time and self. Notably, psilocybin led to a persistent decrease in connectivity between the anterior hippocampus and cortex, especially the DMN, lasting weeks but normalizing after six months, potentially explaining its pro-plasticity and anti-depressant effects.