Depressive Disorder, MajorPhase 3uAspireNCT06308653
Psilocybin for Major Depressive Disorder (MDD)
A Phase 3 study testing Psilocybin 25 mg, Psilocybin 5 mg and Psychosocial Support in people with Depressive Disorder, Major, run by Usona Institute at 29 sites in United States.
Trial summary
Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depressive Disorder, Major
- What is being tested?
- Psilocybin 25 mg, Psilocybin 5 mg and Psychosocial Support
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 238 participants
- Where
- 29 sitesUnited States
- Study dates
- 13 Mar 2024to 30 Jan 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥18 years old.
- Able to swallow capsules.
- If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study.
- Meet the DSM-5-TR criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of at least a 60-day duration at the time of Screening.
- Have at least moderate severity of depression symptoms at Screening and Trial Baseline.
Who cannot join
- Participants who are pregnant, who intend to become pregnant during the trial, or who are currently nursing.
- Have any of the following cardiovascular conditions: coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, clinically-relevant valvular heart disease, pulmonary hypertension, myocardial infarction, a clinically significant ECG abnormality, or tachycardia.
- Have elevated blood pressure.
- Have neurological conditions such as stroke, including transient ischemic attack, epilepsy, neurodegenerative disease (e.g., dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, etc.), or brain tumor.
- Have severe hepatic or renal impairment.
- Have uncontrolled diabetes mellitus or unstable existing thyroid disorder.
Show all 11Show fewer
- Are hepatitis or HIV positive.
- Have a positive urine drug test for illicit, non-prescribed, or prohibited substances.
- Meet DSM-5-TR criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features ,bipolar disorder (types 1 or 2), antisocial personality disorder, borderline personality disorder or moderate or severe alcohol or drug use disorder
- Meet DSM-5-TR criteria for active post-traumatic stress disorder within 6 months prior to Screening.
- Have a first-degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar I disorder.
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
United States29 sites
University of New Mexico (UNM) Interdisciplinary Substance Use and Brain Injury (ISUBI) Center
Albuquerque, New Mexico, 87106
Emory University
Atlanta, Georgia, 30329
Johns Hopkins School of Medicine, Center for Psychedelic and Consciousness Research
Baltimore, Maryland, 21224
Seattle Neuropsychiatric Treatment Center
Bellevue, Washington, 98004
University of Alabama Clinical Research Unit
Birmingham, Alabama, 35209
Great Lakes Clinical Trials
Chicago, Illinois, 60640
CenExel iResearch, LLC
Decatur, Georgia, 30030
Mountain View Clinical Research
Denver, Colorado, 80209
Cedar Clinical Research
Draper, Utah, 84020
Preferred Research Partners-NWA, LLC
Fayetteville, Arkansas, 72703
Clinical Neuroscience Solutions Inc.
Jacksonville, Florida, 32256
Kadima Neuropsychiatry Institute
La Jolla, California, 92037
Innovative Clinical Research, Inc.
Lauderhill, Florida, 33319
Preferred Research Partners, Inc.
Little Rock, Arkansas, 72211
West LA VA Medical Center - Mental Health Department
Los Angeles, California, 90073
Cedar Clinical Research, Inc.
Murray, Utah, 84107
Connecticut Mental Health Center, Yale University
New Haven, Connecticut, 06519
NYU Clinical & Translational Science Institute
New York, New York, 10016
VA Nebraska Western Iowa Health Care System
Omaha, Nebraska, 68105
Clinical Neuroscience Solutions, Inc.
Orlando, Florida, 32801
AIM Trials, LLC
Plano, Texas, 75093
Global Medical Institutes, LLC; Princeton Medical Institute
Princeton, New Jersey, 08540
Sunstone Medical PC
Rockville, Maryland, 20850
Clinical Trials of Texas, LLC
San Antonio, Texas, 78229
Pacific Neuroscience Institute (PNI) at Saint John's Physician Partners
Santa Monica, California, 90404
Psychedelic Science Institute
Santa Monica, California, 90404
Washington University School of Medicine
St Louis, Missouri, 63110
Bronx Veterans Research Foundation at the James J. Peters VAMC
The Bronx, New York, 10468
VA Portland Health Care System
Vancouver, Washington, 98661
About this study
Official title: A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Psilocybin in Adults With Major Depressive Disorder (MDD)
Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Participants will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo.
The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the difference between groups in change in depressive symptoms from Baseline to Day 43 post-dose, and to characterize the durability of initial treatment effect and subsequent response to optional Psilocybin 25 mg re-administration(s) during the 1-year Follow-up Period.
Read the detailed description
Double-blind Period:
Participants who show stable depression symptoms between Screening and Trial Baseline will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo.
Investigational Product (IP) will be administered in the context of a "Set and Setting" (SaS) Protocol for psychosocial support, comprised of 1) a period of preparation with Facilitators prior to dosing; 2) administration of IP in an aesthetically pleasing room under the supervision of two Facilitators; and 3) post-dose integration sessions during which participants will discuss their dosing experience with the Facilitators.
Trial outcome measures will assess depressive symptoms, functional disability, health-related quality of life, and clinical global impression of disease severity.
Long-term Follow-up Period:
After the initial 6-week Double-blind Period and completion of the post-dosing Trial Day 43 assessments, all participants will proceed into a 1-year Follow-up Period.
During the 1-year Follow-up Period, participants will be followed regularly by clinic staff to assess MDD symptom severity, functional disability, and health-related quality of life; long-term safety data will also be collected. In addition to scheduled clinic visits, clinic staff will contact participants by telephone every two weeks to assess for changes in MDD symptom severity, concomitant medications, adverse events (AEs), and suicidal ideation and behavior.
Participants who meet the pre-defined MDD severity criteria and meet all re-administration eligibility criteria may be offered re-administration(s) of open-label Psilocybin 25 mg administered under a "Set and Setting" (SaS) Protocol. Psychosocial support, including psychoeducation, is also incorporated in the long-term Follow-up Period.
- Conditions
- Depressive Disorder, Major
- Being tested
- Psilocybin 25 mg, Inactive Placebo, Psilocybin 5 mg, Psychosocial Support
- Keywords
- Psilocybin, Psychedelic, Depression, Major Depressive Disorder, MDD, Psychosocial, Psychoeducation, Set and Setting
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin 25 mgDrug
Also called Psilocybine, Psilocibin, Indocybin
The Psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of Psilocybin.
Inactive PlaceboDrug
Also called Microcrystalline Cellulose (MCC), Placebo
The inactive placebo is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of Microcrystalline Cellulose (MCC). The MCC is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use.
Psilocybin 5 mgDrug
Also called Psilocybine, Psilocibin, Indocybin, Active Comparator
The Psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active comparator is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 5 mg of Psilocybin.
Psychosocial SupportBehavioural
Psychosocial Support, including psychoeducation, begins after the Double-blind Period and continues throughout the 1-year Follow-up Period in order to enhance participant safety and maximize retention for the entire trial duration.
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin 25 mg | Experimental | During the Double-blind Period, participants randomized to receive Psilocybin 25 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol.
The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. Receives: Drug: Psilocybin 25 mg |
| Psilocybin 5 mg | Active comparator | During the Double-blind Period, participants randomized to receive Psilocybin 5 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol.
The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. Receives: Drug: Psilocybin 5 mg |
| Inactive Placebo | Placebo comparator | During the Double-blind Period, participants randomized to receive inactive placebo will receive a single dose of Microcrystalline Cellulose (MCC) 25 mg administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol.
The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. Receives: Drug: Inactive Placebo |
| Long-Term Follow-Up | Other | After the initial 6-week Double-blind Period, all participants will proceed to a 1-year Follow-up Period. Participants will be followed via in-clinic visits and telephone visits during which clinic staff will assess changes in MDD symptom severity and safety measures including concomitant medications, adverse events (AEs), and suicidal ideation and behavior.
Participants will also engage in group psychosocial support sessions, including psychoeducation, throughout this period.
Participants may also be eligible to receive open-label re-administration(s) of Psilocybin 25 mg under the "Set and Setting" (SaS) Protocol if re-administration eligibility criteria are met. Receives: Drug: Psilocybin 25 mg; Behavioral: Psychosocial Support |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Trial Day 43
The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The total (composite) MADRS score is used as the endpoint.
Measured: From Trial Baseline to Trial Day 43
Secondary outcomes (2)
Change in central rater Clinical Global Impression-Severity (CGI-S) total score from Baseline to Trial Day 43
The CGI-S is a 7-point scale, with a minimum score of 1 and a maximum score of 7, with higher scores representing more severe illness, that assesses the global severity of the participant's illness at the time of assessment relative to the clinician's past experience with patients who have the same diagnosis.
Measured: From Trial Baseline to Trial Day 43
Change in on-site rater administered Sheehan Disability Scale (SDS) score from Baseline to post-dose Day 43
The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors in the patient's life are impaired by psychiatric symptoms, including depression. The SDS total score ranges from 0 to 30 with higher representing greater functional disability.
Measured: From Trial Baseline to Trial Day 43
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2024
- Study start13 Mar 2024
- Primary completion5 Jan 2026
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- 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
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to receive Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo under double-blind conditions. After the initial 6-week Double-blind Period, all participants will proceed into a 1-year Follow-up Period. During this 1-year Follow-up Period, eligible participants who meet pre-determined criteria may be offered open-label Psilocybin 25 mg in the context of a "Set and Setting" (SaS) Protocol.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 238 participants (actual)
Sponsor and investigators
- Lead sponsor
- Usona Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charles Raison, MD, Study chair, Usona Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06308653
- Sponsor's protocol ID
- PSIL301
- Acronym
- uAspire
- Status last verified
- Oct 2026
- First submitted
- 6 Mar 2024
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Raison CL, Sanacora G, Woolley J, Heinzerling K, Dunlop BW, Brown RT, Kakar R, Hassman M, Trivedi RP, Robison R, Gukasyan N, Nayak SM, Hu X, O'Donnell KC, Kelmendi B, Sloshower J, Penn AD, Bradley E, Kelly DF, Mletzko T, Nicholas CR, Hutson PR, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis MC, Nelson-Douthit C, Wilson S, Brown C, Linton W, Ross S, Griffiths RR. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):843-853. doi: 10.1001/jama.2023.14530.
PubMed 37651119Palitsky R, Maples-Keller JL, Peacock C, Dunlop BW, Mletzko T, Grant GH, Raison CL, Chao S, Shub I, Mendelbaum-Kweller M, Smolyar L, Kaplan DM, Rothbaum BO, Zarrabi AJ. A critical evaluation of psilocybin-assisted therapy protocol components from clinical trial patients, facilitators, and caregivers. Psychotherapy (Chic). 2025 Sep;62(3):348-362. doi: 10.1037/pst0000551. Epub 2025 Jan 13.
PubMed 39804360
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Psilocybin in Adults With Major Depressive Disorder (MDD)
- ClinicalTrials.gov ID
- NCT06308653
- Acronym / sponsor ID
- uAspire / PSIL301
- Conditions
- Depressive Disorder, Major
- Keywords
- Psilocybin, Psychedelic, Depression, Major Depressive Disorder, MDD, Psychosocial, Psychoeducation, Set and Setting
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 238 participants (actual)
- Lead sponsor
- Usona InstituteUniversity, hospital or other
- Study start
- 13 Mar 2024 (actual)
- Primary completion
- 5 Jan 2026 (actual)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 13 Mar 2024 (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.
Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Participants will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo.
The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the difference between groups in change in depressive symptoms from Baseline to Day 43 post-dose, and to characterize the durability of initial treatment effect and subsequent response to optional Psilocybin 25 mg re-administration(s) during the 1-year Follow-up Period.
Detailed description
Double-blind Period:
Participants who show stable depression symptoms between Screening and Trial Baseline will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo.
Investigational Product (IP) will be administered in the context of a "Set and Setting" (SaS) Protocol for psychosocial support, comprised of 1) a period of preparation with Facilitators prior to dosing; 2) administration of IP in an aesthetically pleasing room under the supervision of two Facilitators; and 3) post-dose integration sessions during which participants will discuss their dosing experience with the Facilitators.
Trial outcome measures will assess depressive symptoms, functional disability, health-related quality of life, and clinical global impression of disease severity.
Long-term Follow-up Period:
After the initial 6-week Double-blind Period and completion of the post-dosing Trial Day 43 assessments, all participants will proceed into a 1-year Follow-up Period.
During the 1-year Follow-up Period, participants will be followed regularly by clinic staff to assess MDD symptom severity, functional disability, and health-related quality of life; long-term safety data will also be collected. In addition to scheduled clinic visits, clinic staff will contact participants by telephone every two weeks to assess for changes in MDD symptom severity, concomitant medications, adverse events (AEs), and suicidal ideation and behavior.
Participants who meet the pre-defined MDD severity criteria and meet all re-administration eligibility criteria may be offered re-administration(s) of open-label Psilocybin 25 mg administered under a "Set and Setting" (SaS) Protocol. Psychosocial support, including psychoeducation, is also incorporated in the long-term Follow-up Period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Participants will be randomized to receive Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo under double-blind conditions. After the initial 6-week Double-blind Period, all participants will proceed into a 1-year Follow-up Period. During this 1-year Follow-up Period, eligible participants who meet pre-determined criteria may be offered open-label Psilocybin 25 mg in the context of a "Set and Setting" (SaS) Protocol.
| Arm | Type | Receives |
|---|---|---|
| Psilocybin 25 mg | Experimental | Drug: Psilocybin 25 mgDuring the Double-blind Period, participants randomized to receive Psilocybin 25 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. |
| Psilocybin 5 mg | Active comparator | Drug: Psilocybin 5 mgDuring the Double-blind Period, participants randomized to receive Psilocybin 5 mg will receive a single dose administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. |
| Inactive Placebo | Placebo comparator | Drug: Inactive PlaceboDuring the Double-blind Period, participants randomized to receive inactive placebo will receive a single dose of Microcrystalline Cellulose (MCC) 25 mg administered orally as a capsule and taken with water, along with the "Set and Setting" (SaS) Protocol. The "Set and Setting" (SaS) Protocol includes preparatory meetings with two Facilitators prior to dosing, a 7-10 hour dosing session in a comfortable room under the supervision of the same two Facilitators, and 4 hours of post-dose integration sessions with Facilitators. During the dosing session, participants are encouraged to wear eyeshades and listen to a curated playlist on headphones. |
| Long-Term Follow-Up | Other | Drug: Psilocybin 25 mg, Behavioral: Psychosocial SupportAfter the initial 6-week Double-blind Period, all participants will proceed to a 1-year Follow-up Period. Participants will be followed via in-clinic visits and telephone visits during which clinic staff will assess changes in MDD symptom severity and safety measures including concomitant medications, adverse events (AEs), and suicidal ideation and behavior. Participants will also engage in group psychosocial support sessions, including psychoeducation, throughout this period. Participants may also be eligible to receive open-label re-administration(s) of Psilocybin 25 mg under the "Set and Setting" (SaS) Protocol if re-administration eligibility criteria are met. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults ≥18 years old.
- Able to swallow capsules.
- If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study.
- Meet the DSM-5-TR criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of at least a 60-day duration at the time of Screening.
- Have at least moderate severity of depression symptoms at Screening and Trial Baseline.
Key exclusion criteria (11 listed)
- Participants who are pregnant, who intend to become pregnant during the trial, or who are currently nursing.
- Have any of the following cardiovascular conditions: coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, clinically-relevant valvular heart disease, pulmonary hypertension, myocardial infarction, a clinically significant ECG abnormality, or tachycardia.
- Have elevated blood pressure.
- Have neurological conditions such as stroke, including transient ischemic attack, epilepsy, neurodegenerative disease (e.g., dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, etc.), or brain tumor.
- Have severe hepatic or renal impairment.
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 |
|---|---|---|
| Psilocybin 25 mgAlso: Psilocybine, Psilocibin, IndocybinThe Psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of Psilocybin. | Drug | Long-Term Follow-Up, Psilocybin 25 mg |
| Inactive PlaceboAlso: Microcrystalline Cellulose (MCC), PlaceboThe inactive placebo is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of Microcrystalline Cellulose (MCC). The MCC is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. | Drug | Inactive Placebo |
| Psilocybin 5 mgAlso: Psilocybine, Psilocibin, Indocybin, Active ComparatorThe Psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active comparator is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 5 mg of Psilocybin. | Drug | Psilocybin 5 mg |
| Psychosocial SupportPsychosocial Support, including psychoeducation, begins after the Double-blind Period and continues throughout the 1-year Follow-up Period in order to enhance participant safety and maximize retention for the entire trial duration. | Behavioural | Long-Term Follow-Up |
Primary outcome
Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Trial Day 43
Time frame: From Trial Baseline to Trial Day 43
The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The total (composite) MADRS score is used as the endpoint.
2 secondary outcomes
Change in central rater Clinical Global Impression-Severity (CGI-S) total score from Baseline to Trial Day 43
Time frame: From Trial Baseline to Trial Day 43
Change in on-site rater administered Sheehan Disability Scale (SDS) score from Baseline to post-dose Day 43
Time frame: From Trial Baseline to Trial Day 43
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Background: PubMed 37651119Raison CL, Sanacora G, Woolley J, Heinzerling K, Dunlop BW, Brown RT, Kakar R, Hassman M, Trivedi RP, Robison R, Gukasyan N, Nayak SM, Hu X, O'Donnell KC, Kelmendi B, Sloshower J, Penn AD, Bradley E, Kelly DF, Mletzko T, Nicholas CR, Hutson PR, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis MC, Nelson-Douthit C, Wilson S, Brown C, Linton W, Ross S, Griffiths RR. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):843-853. doi: 10.1001/jama.2023.14530.
- Derived from this study: PubMed 39804360Palitsky R, Maples-Keller JL, Peacock C, Dunlop BW, Mletzko T, Grant GH, Raison CL, Chao S, Shub I, Mendelbaum-Kweller M, Smolyar L, Kaplan DM, Rothbaum BO, Zarrabi AJ. A critical evaluation of psilocybin-assisted therapy protocol components from clinical trial patients, facilitators, and caregivers. Psychotherapy (Chic). 2025 Sep;62(3):348-362. doi: 10.1037/pst0000551. Epub 2025 Jan 13.
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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.
Charles Raison, MD study chair
Usona Institute
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Psilocybin 25 mg, Psilocybin 5 mg and Psychosocial Support in people with Depressive Disorder, Major, run by Usona Institute at 29 sites 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 5 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites 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. Some participants in this study may receive a placebo. 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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Trial Day 43 (time frame: From Trial Baseline to Trial Day 43). 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 NCT06308653, which also lists 2 linked publications.
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 21 Oct 2026.