PsilocybinEarly Phase 1Psilocybin PFMNCT04501653

Precision Functional Brain Mapping in Psilocybin

A Early Phase 1 study testing Psilocybin and Methylphenidate in people with Psilocybin, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Psilocybin
What is being tested?: Psilocybin and Methylphenidate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 1 siteUnited States
Study dates: 1 Jun 2021to 19 Mar 2023
Phase: Early Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

men and woman between 18 and 40 years of age;
Have used a psychedelic substance within the previous 5 years but not within the last 6 months
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);
Able to provide informed consent.

Who cannot join

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);
No prior exposure to classic psychedelics (psilocybin, LSD, ayahuasca, mescaline);
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);
Use of psychotropic medication during the study;
Presence of contraindications to MRI scanning (implantable devices, bone hardware, IUD).
Prior adverse reactions to psychedelics, based on the Challenging Experiences Questionnaire administered during initial screening

Trial locations and contacts

1 site in 1 country.

United States1 site

Washington University
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Precision Functional Brain Mapping to Understand the Mechanisms of Psilocybin

Read the 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:

Extended functional magnetic resonance imaging (fMRI) image acquisition
Aggressive data cleaning
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
Being tested: Psilocybin, Methylphenidate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PsilocybinDrug
Also called psilocin
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.
MethylphenidateDrug
Also called Metadate, Methylin, Ritalin, Concerta
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.

Study groups in NCT04501653
Study group	Role	What they receive
Psilocybin first	Experimental	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. Receives: Drug: Psilocybin; Drug: Methylphenidate
Methylphenidate first	Active comparator	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. Receives: Drug: Psilocybin; Drug: Methylphenidate

What is being measured

The primary outcome is the main question the study is designed to answer.

Functional Connectivity
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.
Measured: 1 week

Secondary outcomes (2)

Mystical Experiences
Measured using Persisting Effects Questionnaire
Measured: 1 week
Personality Change
Measured using International Personality Item Pool-Five-Factor Model
Measured: 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 202119 Mar 2023

First posted6 Aug 2020
Study start1 Jun 2021
Primary completion19 Mar 2023
Study completion19 Mar 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for PsilocybinStudies of the same condition, open and under way.
More trials run by Washington University School of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
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 blind
Who is masked: Participant
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04501653
Sponsor's protocol ID: 202002165
Other IDs: GF0010787
Acronym: Psilocybin PFM
Status last verified: Oct 2024
First submitted: 3 Aug 2020
Last updated: 31 Oct 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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The Impact of Dose on the Impairing, Intoxicating, and Abuse-Related Effects of Psilocybin
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NeuroGuard: Psilocybin Trial for Preventing Chemo-induced Neuropathy
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RecruitingPhase 1
PRoMiSS: Psilocybin and the Role of Music in Set and Setting
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Psilocybin-Assisted Psychotherapy in Patients With Advanced Cancer on Maintenance Therapy
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All Psilocybin trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Precision Functional Brain Mapping to Understand the Mechanisms of Psilocybin
ClinicalTrials.gov ID: NCT04501653
Acronym / sponsor ID: Psilocybin PFM / 202002165
Conditions: Psilocybin
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Study start: 1 Jun 2021 (actual)
Primary completion: 19 Mar 2023 (actual)
Study completion: 19 Mar 2023 (actual)
First posted: 6 Aug 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Functional connectivity will be measured using the following PFM approach:

Extended functional magnetic resonance imaging (fMRI) image acquisition
Aggressive data cleaning
Analysis designed to examine functional brain connectivity at the individual level

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind (participant)
Number of arms: 2
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.

Arm	Type	Receives
Psilocybin first	Experimental	Drug: Psilocybin, Drug: MethylphenidateParticipants 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.
Methylphenidate first	Active comparator	Drug: Psilocybin, Drug: MethylphenidateParticipants 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.

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

men and woman between 18 and 40 years of age;
Have used a psychedelic substance within the previous 5 years but not within the last 6 months
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);
Able to provide informed consent.

Key exclusion criteria (6 listed)

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);
No prior exposure to classic psychedelics (psilocybin, LSD, ayahuasca, mescaline);
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);
Use of psychotropic medication during the study;
Presence of contraindications to MRI scanning (implantable devices, bone hardware, IUD).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PsilocybinAlso: psilocinPsilocybin 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.	Drug	Methylphenidate first, Psilocybin first
MethylphenidateAlso: Metadate, Methylin, Ritalin, ConcertaMethylphenidate 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.	Drug	Methylphenidate first, Psilocybin first

Primary outcome

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.

2 secondary outcomes

Mystical Experiences
Time frame: 1 week
Personality Change
Time frame: 1 week

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2025.
Individual participant dataSharing planned: No

Related trials for Psilocybin

Not yet recruitingPhase 2
Psilocybin-Assisted Physical Therapy in Chronic Low Back Pain
Chronic Low Back Pain (CLBP), Physical Therapy
Not yet recruitingPhase 1
The Impact of Dose on the Impairing, Intoxicating, and Abuse-Related Effects of Psilocybin
Psilocybin Intoxication
Not yet recruitingPhase 2
NeuroGuard: Psilocybin Trial for Preventing Chemo-induced Neuropathy
Psilocybin, Neuropathy
RecruitingPhase 1
PRoMiSS: Psilocybin and the Role of Music in Set and Setting
Psilocybin, Music Intervention
RecruitingPhase 2
Psilocybin-Assisted Psychotherapy in Patients With Advanced Cancer on Maintenance Therapy
Depression, Anxiety, Psilocybin-Assisted Psychotherapy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Psilocybin and Methylphenidate in people with Psilocybin, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Functional Connectivity (time frame: 1 week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04501653.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2025; AzTrials last refreshed its copy on 27 Oct 2026.