Psilocybin-Assisted Therapy as a Treatment for Depression

NCT07582120 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 202603029
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Depression

Keywords

depression; psilocybin; fMRI; biomarker; psychedelics

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  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

Study Arms (1)

25mg Open Label dose of synthetic psilocybin

EXPERIMENTAL

Drug: Psilocybin (Usona Institute)

Interventions

Psilocybin (Usona Institute) DRUG

Capsule containing 25 mg of synthetic psilocybin

25mg Open Label dose of synthetic psilocybin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Participants of childbearing potential must agree to practice 2 forms of effective birth control throughout the duration of the study
• Females of childbearing potential must have a negative urine pregnancy test at Screening and prior to dosing on Dosing Day
• Diagnosis of depression at Screening via the SCID-5-CT interview and MADRS score of ≥7
• 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

You may not qualify if:

• Unable to read or understand English
• Is currently pregnant or breastfeeding, or plan to become pregnant or breastfeed within the study period
• 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
• 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:
• 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.
• 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).
• Has a primary psychotic disorder diagnosis
• Has a first-degree relative with a known history of a psychotic disorder
• Meets criteria for substance use disorder or diagnosis of substance use disorder within 6 months prior to Screening
• 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
• Is at risk for hypertensive crisis defined as:
• BP at Screening AND Baseline \>140/90 mmHG
• BP on Dosing Day prior to dosing \>140/90 mmHG
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Siegel JS, Subramanian S, Perry D, Kay BP, Gordon EM, Laumann TO, Reneau TR, Metcalf NV, Chacko RV, Gratton C, Horan C, Krimmel SR, Shimony JS, Schweiger JA, Wong DF, Bender DA, Scheidter KM, Whiting FI, Padawer-Curry JA, Shinohara RT, Chen Y, Moser J, Yacoub E, Nelson SM, Vizioli L, Fair DA, Lenze EJ, Carhart-Harris R, Raison CL, Raichle ME, Snyder AZ, Nicol GE, Dosenbach NUF. Psilocybin desynchronizes the human brain. Nature. 2024 Aug;632(8023):131-138. doi: 10.1038/s41586-024-07624-5. Epub 2024 Jul 17.

  PMID: 39020167 BACKGROUND

MeSH Terms

Conditions

Depression

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Central Study Contacts

Dawnita Reathaford

CONTACT

314-532-5939; dawnita@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 5, 2026
• First Posted: May 12, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)