Precision Functional Brain Mapping in Psilocybin

NCT ID: NCT04501653

Last Updated: 2025-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2023-03-19

Brief Summary

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.

Detailed Description

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.

Conditions

Psilocybin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Psilocybin first

Participants will receive 25 mg of psilocybin at the first of two neuroimaging sessions, taken orally in capsule form. Participants in this arm will receive the control drug (methylphenidate) at their second drug exposure neuroimaging session.

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

Psilocybin is a naturally occurring psychedelic compound produced by psilocybin mushrooms, and has been shown to have antidepressant and anti-anxiety effects after one dose of 25 mg. Common side effects are slight elevations in blood pressure and heart rate. Participants will be randomized to receive either psilocybin or control at two separate imaging timepoints in this study.

Methylphenidate

Intervention Type: DRUG

Methylphenidate is a stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and is used as an active control for this study because it is metabolized similarly to psilocybin and has similar effects on heart rate and blood pressure. Participants will be randomized to receive either psilocybin or control at two separate imaging timepoints in this study.

Methylphenidate first

Participants in this group will be randomized to receive 40 mg of methylphenidate at the first of two neuroimaging sessions, taken orally in capsule form. Participants in this arm will receive the active comparator (psilocybin) at their second drug exposure neuroimaging session.

Group Type: ACTIVE_COMPARATOR

Psilocybin

Intervention Type: DRUG

Psilocybin is a naturally occurring psychedelic compound produced by psilocybin mushrooms, and has been shown to have antidepressant and anti-anxiety effects after one dose of 25 mg. Common side effects are slight elevations in blood pressure and heart rate. Participants will be randomized to receive either psilocybin or control at two separate imaging timepoints in this study.

Methylphenidate

Intervention Type: DRUG

Methylphenidate is a stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and is used as an active control for this study because it is metabolized similarly to psilocybin and has similar effects on heart rate and blood pressure. Participants will be randomized to receive either psilocybin or control at two separate imaging timepoints in this study.

Interventions

Psilocybin

Psilocybin is a naturally occurring psychedelic compound produced by psilocybin mushrooms, and has been shown to have antidepressant and anti-anxiety effects after one dose of 25 mg. Common side effects are slight elevations in blood pressure and heart rate. Participants will be randomized to receive either psilocybin or control at two separate imaging timepoints in this study.

Intervention Type: DRUG

Methylphenidate

Methylphenidate is a stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and is used as an active control for this study because it is metabolized similarly to psilocybin and has similar effects on heart rate and blood pressure. Participants will be randomized to receive either psilocybin or control at two separate imaging timepoints in this study.

Intervention Type: DRUG

Other Intervention Names

psilocin; Metadate, Methylin, Ritalin, Concerta

Eligibility Criteria

Inclusion Criteria

1. men and woman between 18 and 40 years of age;

2. Have used a psychedelic substance within the previous 5 years but not within the last 6 months

3. No active psychiatric conditions requiring treatment with psychotropic medications (may be included if psychiatric condition is stable and participant is willing to discontinue medication for 1 month prior to participation with permission from their treating provider);

4. Able to provide informed consent.

Exclusion Criteria

1. Presence of medical conditions that may confound results of imaging study or that are contraindications to psilocybin exposure (e.g. neurological, renal, hypertension, metabolic or cardiovascular disease or pregnancy);

2. No prior exposure to classic psychedelics (psilocybin, LSD, ayahuasca, mescaline);

3. Presence of psychiatric conditions that may confound interpretation of results or that are contraindications to psilocybin exposure (e.g. major mood disorder, current substance use disorder, personal or immediate family history (parents, siblings) of any schizophrenia spectrum disorders);

4. Use of psychotropic medication during the study;

5. Presence of contraindications to MRI scanning (implantable devices, bone hardware, IUD).

6. Prior adverse reactions to psychedelics, based on the Challenging Experiences Questionnaire administered during initial screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Ginger E Nicol

Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Washington University

St Louis, Missouri, United States

Countries

United States

Other Identifiers

GF0010787

Identifier Type: OTHER

Identifier Source: secondary_id

202002165

Identifier Type: -

Identifier Source: org_study_id