<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04501653</url>
  </required_header>
  <id_info>
    <org_study_id>202002165</org_study_id>
    <nct_id>NCT04501653</nct_id>
  </id_info>
  <brief_title>Precision Functional Brain Mapping in Psilocybin</brief_title>
  <acronym>Psilocybin PFM</acronym>
  <official_title>Precision Functional Brain Mapping to Understand the Mechanisms of Psilocybin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This project will employ functional brain imaging to study the mechanism and immediate and&#xD;
      long-term effects of psilocybin, a serotonin receptor 2A agonist, on cortical and&#xD;
      cortico-subcortical brain networks in healthy adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Psilocybin shows promise as a safe, transformational therapeutic across several psychiatric&#xD;
      conditions. However, little is know about its mechanism of action. This study aims to&#xD;
      establish a neuroimaging paradigm for use in future clinical research testing the&#xD;
      effectiveness of psilocybin in various clinical applications.&#xD;
&#xD;
      In this study, we will assess both acute (during psilocybin exposure) and sustained (one week&#xD;
      post-exposure) effects of 5-HT2A receptor agonism on brain circuits using resting state&#xD;
      functional connectivity and precision functional mapping (PFM). Using a randomized,&#xD;
      controlled crossover study design, a small number of healthy volunteers will receive either&#xD;
      psilocybin or methylphenidate (MTP) and will undergo MRI (structural, task, blood flow,&#xD;
      extended resting state). After two weeks, participants will return for a second exposure with&#xD;
      the alternate of what they received in the first session. This study involves up to five&#xD;
      separate imaging sessions.&#xD;
&#xD;
      Functional connectivity will be measured using the following PFM approach:&#xD;
&#xD;
        1. Extended functional magnetic resonance imaging (fMRI) image acquisition&#xD;
&#xD;
        2. Aggressive data cleaning&#xD;
&#xD;
        3. Analysis designed to examine functional brain connectivity at the individual level&#xD;
&#xD;
      This will allow us to map the effects of 5-HT2A receptor agonism on cortical and&#xD;
      cortico-subcortical brain networks at the individual level with precision that is&#xD;
      unparalleled in the current literature. This is the first step in developing a precision&#xD;
      neuroimaging approach for mechanistic understanding of psilocybin's therapeutic effects.&#xD;
&#xD;
      If successful, this pharmacoimaging paradigm will have potential utility across psychiatric&#xD;
      conditions, allowing us to better understand whether and how psilocybin might &quot;bend the&#xD;
      curve&quot; in treatment course, preventing persistent suffering, disability, and suicide.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 1, 2021</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <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 &quot;between&quot; 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.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
    <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).</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Functional Connectivity</measure>
    <time_frame>1 week</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mystical Experiences</measure>
    <time_frame>1 week</time_frame>
    <description>Measured using Persisting Effects Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Personality Change</measure>
    <time_frame>1 week</time_frame>
    <description>Measured using International Personality Item Pool-Five-Factor Model</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">25</enrollment>
  <condition>Psilocybin</condition>
  <arm_group>
    <arm_group_label>Psilocybin first</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methylphenidate first</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Psilocybin</intervention_name>
    <description>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.</description>
    <arm_group_label>Methylphenidate first</arm_group_label>
    <arm_group_label>Psilocybin first</arm_group_label>
    <other_name>psilocin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate</intervention_name>
    <description>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.</description>
    <arm_group_label>Methylphenidate first</arm_group_label>
    <arm_group_label>Psilocybin first</arm_group_label>
    <other_name>Metadate, Methylin, Ritalin, Concerta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. men and woman between 18 and 40 years of age;&#xD;
&#xD;
          2. Have used a psychedelic substance within the previous 5 years but not within the last&#xD;
             6 months&#xD;
&#xD;
          3. No active psychiatric conditions requiring treatment with psychotropic medications&#xD;
             (may be included if psychiatric condition is stable and participant is willing to&#xD;
             discontinue medication for 1 month prior to participation with permission from their&#xD;
             treating provider);&#xD;
&#xD;
          4. Able to provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of medical conditions that may confound results of imaging study or that are&#xD;
             contraindications to psilocybin exposure (e.g. neurological, renal, hypertension,&#xD;
             metabolic or cardiovascular disease or pregnancy);&#xD;
&#xD;
          2. No prior exposure to classic psychedelics (psilocybin, LSD, ayahuasca, mescaline);&#xD;
&#xD;
          3. Presence of psychiatric conditions that may confound interpretation of results or that&#xD;
             are contraindications to psilocybin exposure (e.g. major mood disorder, current&#xD;
             substance use disorder, personal or immediate family history (parents, siblings) of&#xD;
             any schizophrenia spectrum disorders);&#xD;
&#xD;
          4. Use of psychotropic medication during the study;&#xD;
&#xD;
          5. Presence of contraindications to MRI scanning (implantable devices, bone hardware,&#xD;
             IUD).&#xD;
&#xD;
          6. Prior adverse reactions to psychedelics, based on the Challenging Experiences&#xD;
             Questionnaire administered during initial screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Washington University School of Medicine</investigator_affiliation>
    <investigator_full_name>Ginger E Nicol</investigator_full_name>
    <investigator_title>Associate Professor of Psychiatry</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
    <mesh_term>Psilocybin</mesh_term>
    <mesh_term>Psilocin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04501653
org study id: 202002165
nct id: NCT04501653
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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.
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.
primary purpose: Basic Science
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).
measure: Functional Connectivity
time frame: 1 week
description: 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.
measure: Mystical Experiences
time frame: 1 week
description: Measured using Persisting Effects Questionnaire
measure: Personality Change
time frame: 1 week
description: Measured using International Personality Item Pool-Five-Factor Model
arm group label: Psilocybin first
arm group type: Experimental
description: 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.
arm group label: Methylphenidate first
arm group type: Active Comparator
description: 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.
intervention type: Drug
intervention name: Psilocybin
description: 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.
arm group label: Methylphenidate first
arm group label: Psilocybin first
other name: psilocin
intervention type: Drug
intervention name: Methylphenidate
description: 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.
arm group label: Methylphenidate first
arm group label: Psilocybin first
other name: Metadate, Methylin, Ritalin, Concerta
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Washington University School of Medicine
investigator full name: Ginger E Nicol
investigator title: Associate Professor of Psychiatry
mesh term: Methylphenidate
mesh term: Psilocybin
mesh term: Psilocin
sharing ipd: No