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Precision Functional Brain Mapping in Psilocybin (Psilocybin PFM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04501653
Recruitment Status : Active, not recruiting
First Posted : August 6, 2020
Last Update Posted : November 28, 2022
Sponsor:
Information provided by (Responsible Party):
Ginger E Nicol, Washington University School of Medicine

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
Psilocybin Drug: Psilocybin Drug: Methylphenidate 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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.
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 : June 1, 2021
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: Metadate, Methylin, Ritalin, Concerta




Primary Outcome Measures :
  1. Functional Connectivity [ Time Frame: 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 [ Time Frame: 1 week ]
    Measured using Persisting Effects Questionnaire

  2. Personality Change [ Time Frame: 1 week ]
    Measured using International Personality Item Pool-Five-Factor Model



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04501653


Locations
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United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
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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: August 6, 2020    Key Record Dates
Last Update Posted: November 28, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Methylphenidate
Psilocybin
Psilocin
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Hallucinogens
Psychotropic Drugs