Psilocybin-Assisted Therapy as a Treatment for Depression

May 18, 2026 updated by: Ginger E Nicol, Washington University School of Medicine

A Pilot Mechanistic Study of Psilocybin-Assisted Therapy as a Treatment for Depression

Depression is the leading cause of disability worldwide, affecting an estimated 300 million people. Despite available treatments, response rates remain modest, and treatment resistance is common. Novel treatments are needed that act rapidly, produce lasting effects and work differently than existing antidepressants.

In clinical trials, psilocybin has shown promise as a treatment for depression due to its rapid onset of antidepressant effects and sustained benefits.

This study will use MRI scanning of the brain and other biological measures (biomarkers) to investigate how psilocybin affects brain activity and psychological flexibility before, during, and after receiving psilocybin in participants with depressive symptoms.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age > 18 years
  2. Participants of childbearing potential must agree to practice 2 forms of effective birth control throughout the duration of the study
  3. Females of childbearing potential must have a negative urine pregnancy test at Screening and prior to dosing on Dosing Day
  4. Diagnosis of depression at Screening via the SCID-5-CT interview and MADRS score of ≥7
  5. Have an identified support person Agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing

Exclusion Criteria:

  1. Unable to read or understand English
  2. Is currently pregnant or breastfeeding, or plan to become pregnant or breastfeed within the study period

  3. Has had Electroconvulsive Therapy, Transmagnetic Stimulation, Vagus Nerve Stimulation or Deep Brain Stimulation treatment within the last 12 months

    a. Participants with VNS or DBS devices in place- including devices that are inactive or turned off will not be eligible to participate in the imaging portion of the study

  4. Is currently taking a medication on the prohibited medications list, such as heterocyclic (tricyclic, tetracyclic) antidepressants, monoamine oxidase inhibitors (MAOIs), antipsychotic augmentation therapy, or is taking more than one medication for the treatment of depression:

    1. Participants who are taking a single prescription medication for depression must be on a stable, minimally therapeutic/tolerated dose for at least 4 weeks prior to Screening.
    2. Psychostimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) are allowed, if used at a stable dose or pattern for at least 6-weeks prior to Screening and not used on Dosing Day(s).
  5. Has a primary psychotic disorder diagnosis
  6. Has a first-degree relative with a known history of a psychotic disorder
  7. Meets criteria for substance use disorder or diagnosis of substance use disorder within 6 months prior to Screening
  8. Has an unstable medical condition or serious abnormalities of complete blood count, chemistries, or ECG, or taking medications that in the opinion of the study clinician would preclude safe participation in the trial

  9. Is at risk for hypertensive crisis defined as:

    1. BP at Screening AND Baseline >140/90 mmHG
    2. BP on Dosing Day prior to dosing >140/90 mmHG
  10. Has used a serotonergic hallucinogenic substance (e.g., psilocybin, lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine, 3,4-methylenedioxymethamphetamine (MDMA), or other related substances) within 6 months of Screening.
  11. Has a known sensitivity to psychedelic medications
  12. Has a positive urine drug test including amphetamines, barbiturates, buprenorphine, benzodiazepines, cocaine, methamphetamine (unless prescribed), MDMA, methadone, opiates, and phencyclidine (PCP)
  13. Is at high risk for suicide (e.g., active suicidal ideation and or current intent or plan) and unable to be managed safely (i.e., unwilling to be hospitalized)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 25mg Open Label dose of synthetic psilocybin
Drug: Psilocybin (Usona Institute)
Capsule containing 25 mg of synthetic psilocybin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterize ACUTE (~1 week post-dose) and PERSISTING (~30 days post-dose) effects of PAT in depressed adults at two possible administrations on depression symptom severity using the Montgomery-Asberg Depression Rating Scale (MADRS) score.
Time Frame: 1 week and 30 days post-dose for both administration sessions
The MADRS is a 10-item instrument used to assess depression severity. The total MADRS score ranges from 0-60, with higher scores indicating increased severity of depression
1 week and 30 days post-dose for both administration sessions
Characterize ACUTE (~1 week post-dose) and PERSISTING (~30 days post-dose) effects of PAT in depressed adults at two possible administrations on psychological flexibility using the Multidimensional Psychological Flexibility Inventory (MPFI).
Time Frame: 1 week and 30 days post-dose for both administration sessions
The Multidimensional Psychological Flexibility Inventory (MPFI) is scored by averaging 60 items (or 24 in the short form) on a 1-6 scale (1 = "never true", 6 = "always true"). Higher average scores (1-6) indicate higher levels of the trait, with 12 subscales mapping onto psychological flexibility and inflexibility, allowing for detailed, sub-process, or global profiling.
1 week and 30 days post-dose for both administration sessions

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2031

Study Completion (Estimated)

December 1, 2031

Study Registration Dates

First Submitted

May 5, 2026

First Submitted That Met QC Criteria

May 5, 2026

First Posted (Actual)

May 12, 2026

Study Record Updates

Last Update Posted (Actual)

May 20, 2026

Last Update Submitted That Met QC Criteria

May 18, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202603029

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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