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Psilocybin PFM: Precision Functional Brain Mapping in Psilocybin

Sponsor
Washington University School of Medicine (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04501653
Collaborator
(none)
25
Enrollment
1
Location
2
Arms
12.9
Anticipated Duration (Months)
1.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Early Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
25 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Participants will undergo a baseline imaging session, followed by a blinded drug session with psilocybin 25mg, or methylphenidate (MTP) 40mg. Participants will then have a "between" imaging session without medication, followed by another medication imaging session with the agent not used in the first medication session. This will be followed by a final imaging session without medication.Participants will undergo a baseline imaging session, followed by a blinded drug session with psilocybin 25mg, or methylphenidate (MTP) 40mg. Participants will then have a "between" imaging session without medication, followed by another medication imaging session with the agent not used in the first medication session. This will be followed by a final imaging session without medication.
Masking:
Single (Participant)
Masking Description:
Participants will be aware that they are receiving either psilocybin or methylphenidate at each medication imaging session, but will not be told in what order they will receive study medication (psilocybin first versus methylphenidate first).
Primary Purpose:
Basic Science
Official Title:
Precision Functional Brain Mapping to Understand the Mechanisms of Psilocybin
Actual Study Start Date :
Jun 1, 2021
Anticipated Primary Completion Date :
Jun 30, 2022
Anticipated Study Completion Date :
Jun 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: 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.
Other Names:
  • psilocin

    • 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.
    Other Names:
  • Metadate, Methylin, Ritalin, Concerta

    		•
    Active Comparator: 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.

    Drug: 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.
    Other Names:
  • psilocin

    • 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.
    Other Names:
  • Metadate, Methylin, Ritalin, Concerta

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Functional Connectivity [1 week]

      Our overall goal is to use a Functional Connectivity (very long scans to produce individual connectomes) to examine the effects of psilocybin on cortical and cortico- subcortical brain networks that could explain its rapid and sustained behavioral effects.

    Secondary Outcome Measures

    1. Mystical Experiences [1 week]

      Measured using Persisting Effects Questionnaire

    2. Personality Change [1 week]

      Measured using International Personality Item Pool-Five-Factor Model

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 40 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University Saint Louis Missouri United States 63110

    Sponsors and Collaborators

    • Washington University School of Medicine

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ginger E Nicol, Associate Professor of Psychiatry, Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT04501653
    Other Study ID Numbers:
    • 202002165
    First Posted:
    Aug 6, 2020
    Last Update Posted:
    Jun 21, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:
    Methylphenidate
    Psilocybin
    Psilocin

    Study Results

    No Results Posted as of Jun 21, 2022