Recruiting

Phase 3

CYB003A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder

Sponsor:

Cybin IRL Limited

Code:

NCT06793397

Conditions

Major Depressive Disorder (MDD)

Depression in Adults

Depression - Major Depressive Disorder

Depression Disorders

Depression Disorder

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

CYB003

Psychological Support

Study Details

Brief summary:

The purpose of this study is to determine the efficacy, safety and tolerability of CYB003 compared to matching placebo as adjunctive treatment in patients with MDD.

For more information about the EMBRACE study, including participating study locations, and to register your interest in learning more about participation, please visit the study website: https://embrace-mdd-trial.com/

Conditions

Major Depressive Disorder (MDD)

Depression in Adults

Depression - Major Depressive Disorder

Depression Disorders

Depression Disorder

Study ID

NCT06793397

Start date

Dec 10, 2025

Status verified date

Feb, 2026

Completion date

May 8, 2027

Anticipated

Primary completion date

Mar 18, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Participants must meet all the following criteria to be included in the trial:

Age18 to 85 years.
Participant has a diagnosis of MDD (single or recurrent episode as defined by DSM-5 TR \[if single episode, duration of ≥4 weeks and ≤24 months\] and established as per evaluation by the Investigator. The first MDD episode must have occurred prior to age 60.
Moderate to severe depression at Screening and Baseline, independently confirmed.
Participants have been on a stable dose of antidepressant medication (label specified) at an adequate dose in the last 4 weeks prior to Screening and has had an inadequate response (less than 50% improvement), as judged by the Investigator.
Participant has a body mass index (BMI) of 40 kg/m2 or less (BMI ≤40 kg/m2), inclusive, at Screening.
Participant is able to refrain from nicotine use during the dosing session (up to 8 hours).
Participants capable of producing sperm must use a condom plus spermicide during the trial and for 12 weeks after their final dose of trial medication, if their partner is a person of childbearing potential.
Participants of childbearing potential who have a partner capable of producing sperm must agree to use a highly effective method of contraception in combination with the use of a condom plus spermicide during the trial and for 12 weeks after their final dose of trial medication. Such participants must have a negative pregnancy test at Screening and Day 1 prior to dosing.
Participants of non-childbearing potential who are or were capable of producing eggs (ova) must have been postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
Participants have provided written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.

Exclusion Criteria

Participants with any of the following characteristics/conditions will be excluded from trial participation:

Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder, brief psychotic disorder, current or previous history of bipolar disorder, or current borderline personality disorder.
Participants with a medical diagnosis of attention deficit hyperactivity disorder (ADHD) will be excluded if currently taking medication for ADHD.
Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1 (first-degree relatives).
Significant suicide risk within the past 6 months, during the Screening Period, or at Baseline; or (b) suicidal behaviors within 12 months of Screening; or (c) clinical assessment of significant suicidal risk during clinical interview; or (d) non-suicidal self-injury within 12 months of Screening.
Current or previous diagnosis of treatment-resistant MDD, defined as failure to respond to 2 or more antidepressant treatments of 2 different classes given at an adequate dose (label specified) for an adequate duration as judged by the Investigator and clinical interview.
Has had electroconvulsive treatment, transcranial magnetic stimulation, deep brain stimulation, or vagal nerve stimulation for any episode of MDD in the last 6 months.
Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressants, mirtazapine, trazodone, moclobemide, buspirone, or an antipsychotic or mood stabilizer. Note: if receiving these medications are for another indication, they must be discontinued ≥ 14 days or 5 half-lives, whichever is longer, prior to Day 1.
Participant report of (or if available in medical record) exposure to psilocin, or 5-HT2a receptor agonists, or any other psychedelics, such as ayahuasca, mescaline, lysergic acid diethylamide, peyote, or 3,4-methylenedioxymethamphetamine, more than 10 times over the participant's lifetime or any psychedelic use within 12 months prior to Screening.
Participant report of (or if available in medical record) treatment with ketamine or S-ketamine use within 6 months prior to Screening.
Clinically relevant history of abnormal physical health interfering with the trial (including but not limited to, neurological, cardiovascular, respiratory, gastrointestinal \[including dyspepsia or gastroesophageal reflux disease\], hepatic, or renal disorder).
Has hypothyroidism or hyperthyroidism, unless controlled on appropriate medication.
Current diagnosis of uncontrolled hypertension or an arrhythmia, or clinically relevant abnormal results for heart rate.
Participants have a presence or relevant history of organic brain disorders.
Participant is taking or has taken OTC doses of 5-HTP or St John's Wort within prior to trial medication administration.
Donation of blood or plasma within 4 weeks prior to first dosing and until 4 weeks after final dosing.
Participants capable of producing sperm who will not abstain from sperm donation between first dosing and 12 weeks after final dosing.
Participants of childbearing potential who are pregnant, breastfeeding, planning to conceive or unwilling to abstain from egg (ova) donation between first dosing and 12 weeks after final dosing.
History of serotonin syndrome.
Unwilling to consent to audio and video recording of psychological support and dosing sessions.

Study Design

Enrollment

330 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Experimental Arm A CYB003 in 2 of 2 Dosing Sessions

Arm A participants will receive 8 mg of CYB003 in 2 of 2 medicine sessions, approximately three weeks apart. All Arm A participants will continue on their current antidepressants and receive psychological support throughout the study.

experimental: Experimental Arm B CYB003 in 2 of 2 Dosing Sessions

Experimental Arm B participants will receive 16 mg of CYB003 in 2 of 2 medicine sessions, approximately three weeks apart. All Arm B participants will continue on their current antidepressants and receive psychological support throughout the study.

placebo comparator: Placebo Comparator: Arm C Placebo in 2 of 2 Dosing Session

Participants will receive placebo in 2 of 2 medicine sessions, approximately three weeks apart. All Arm C participants will continue on their current antidepressants and receive psychological support throughout the study. Non-responders will be eligible to receive CYB003 in a subsequent extension trial.

Interventions

CYB003

CYB003 is a deuterated psilocin analog.

Psychological Support

Manualized psychological support performed by facilitator.

Primary outcome measure

Montgomery-Asberg Depression Scale (MADRS) [ Time Frame: Screening Day-45, Baseline, Day -1, Day 21, Day 42, Day 63 and Day 84/End of Trial. ]

Central Contacts and Locations

Central contacts

Clinical Development

877-361-4003 clinicaltrialsinfo@cybin.com

Locations

UAB Psychiatry and Behavioral Neurology

Recruiting

Birmingham, Alabama, United States, 35209

Contacts

205-934-2484 psychresearch@uab.edu

Principal Investigator:

Peter Hendricks

Lighthouse Psychiatry

Recruiting

Gilbert, Arizona, United States, 85234

Contacts

Chung Trinh

435-268-5800 ctrinh@neosciclinicalresearch.com

Principal Investigator:

Frank Genova

Behavioral Research Specialists, LLC

Recruiting

Glendale, California, United States, 91206

Contacts

Laisha Uribe

888-255-5798 laisha@brstrials.com

Principal Investigator:

Jesse Carr

CalNeuro Research Group

Recruiting

Los Angeles, California, United States, 90025

Contacts

310-208-7144 info@calneuroresearch.com

Principal Investigator:

Alexander Bystritsky

ATP Clinical Research

Recruiting

Orange, California, United States, 92866

Contacts

Sarah Perkins

949-354-5353 sarahp@pnsoc.com

Principal Investigator:

Gustavo Alva

NRC Research Institute

Recruiting

Orange, California, United States, 92868

Contacts

Christian Ortiz

714-289-1100 cortiz@nrcresearch.com

Principal Investigator:

Daniel Chueh

Psychedelic Science Institute

Recruiting

Santa Monica, California, United States, 90404

Contacts

213-973-7512 trialadmin@psychedelicsci.com

Principal Investigator:

Keith Heinzerling

Yale School of Medicine - Yale Program for Psychedelic Science

Recruiting

New Haven, Connecticut, United States, 06511

Contacts

Daidre Chamberlain

203-693-1591 enact@yale.edu

Terrence Ching

502-612-1127 terence.ching@yale.edu

Principal Investigator:

Ben Kelmendi

CNS Healthcare

Recruiting

Jacksonville, Florida, United States, 32256

Contacts

904-281-5757

Principal Investigator:

John Mark Joyce

Accel Research Sites - Maitland

Recruiting

Maitland, Florida, United States, 32751

Contacts

407-644-1165

Principal Investigator:

Andrea Marrafino

Aqualane Clinical Research

Recruiting

Naples, Florida, United States, 34105

Contacts

Rachel Novella

239-529-6780 Rachel@Aqualaneresearch.com

Principal Investigator:

Matthew Baker

Psych Atlanta

Recruiting

Marietta, Georgia, United States, 30060

Contacts

770-422-2846 research@hightophealth.com

Principal Investigator:

Michael Banov

Rush University

Recruiting

Chicago, Illinois, United States, 60612

Contacts

Stephanie Gutierrez

312-942-8995 stephanie_z_gutierrez@rush.edu

Principal Investigator:

Joshua Eloge

Atlas Psychiatry

Recruiting

New Orleans, Louisiana, United States, 70115

Contacts

Milton Boresoff

504-899-1682 m.boresoff@atlaspsychiatry.com

Principal Investigator:

Nicholas Pejic

Institute for Integrative Therapies

Recruiting

Eden Prairie, Minnesota, United States, 55347

Contacts

Sena Ostwalt

6512808774 sena.ostwalt@iit-mn.com

Principal Investigator:

Manoj Doss

Redbird Research, LLC

Recruiting

Las Vegas, Nevada, United States, 89119

Contacts

702-577-2000 info@redbird-research.com

Principal Investigator:

Jelena Kunovac

Bio Behavioral Health

Recruiting

Toms River, New Jersey, United States, 08755

Contacts

Jessica Sutton

732-244-2299 jessica@bbhnj.com

Principal Investigator:

Ashok Patel

Adams Clinical Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

267-207-2511 info@adamsclinical.com

Principal Investigator:

Cassie Blanchard

Flourish Research Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19462

Contacts

215-614-5606

Principal Investigator:

Rachna Saralkar

Brain Health Consultants and TMS Center

Recruiting

Houston, Texas, United States, 77046

Contacts

713-489-5000 info@brainhealthconsultants.com

Principal Investigator:

Lauren Marangell

Flourish Research San Antonio

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Xavier Martinez

210-949-0122 xmartinez@flourishresearch.com

Andrea Gomez

210-949-0122 agomez@flourishresearch.com

Principal Investigator:

Parke Hedges

Seattle Neuropsychiatric Treatment Center

Recruiting

Seattle, Washington, United States, 98104

Contacts

206-467-6300 research@seattlentc.com

Principal Investigator:

Rebecca Allen

More Information

Sponsor

Cybin IRL Limited

Last update posted

Aug 26, 2026

Last verified

Feb, 2026

Keywords

MDD
Psychedelic
Depression
Major Depressive Disorder
CYB003
CYB003-001
CYB003-002
Psilocybin
psilocin-7438

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Cybin IRL Limited on 2026-08-26.