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

NCT ID: NCT06564818

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-17

Study Completion Date

2026-09-30

Brief Summary

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

Detailed Description

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Conditions

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Major Depressive Disorder

Keywords

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Major Depressive Disorder MDD Psilocybin Psychedelic Psilocin CYB003 CYB003-001 Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Experimental Arm A: CYB003 in 2 of 2 Dosing Sessions

Arm A participants will receive 16 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.

Group Type EXPERIMENTAL

CYB003

Intervention Type DRUG

CYB003 is a Deuterated Psilocin Analog.

Psychological Support

Intervention Type BEHAVIORAL

Manualized psychological support performed by facilitators

Placebo Comparator Arm B: Placebo in 2 of 2 Dosing Sessions

Arm B participants will receive placebo in 2 of 2 Dosing Sessions, approximately three weeks apart. All Arm B 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.

Group Type PLACEBO_COMPARATOR

Psychological Support

Intervention Type BEHAVIORAL

Manualized psychological support performed by facilitators

Placebo

Intervention Type DRUG

Placebo

Interventions

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CYB003

CYB003 is a Deuterated Psilocin Analog.

Intervention Type DRUG

Psychological Support

Manualized psychological support performed by facilitators

Intervention Type BEHAVIORAL

Placebo

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

* Aged 18 to 85 years inclusive, at Screening
* 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.
* Depression is of moderate to severe degree at Screening, independently confirmed by additional clinical assessments
* Participant has been on a stable dose of a single antidepressant medication at an adequate dose (label specified) for an adequate duration in the last 4 weeks prior to Screening and has had an inadequate response (less than 50% improvement), as judged by the Investigator and clinical interviews.
* 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)
* Registered with a healthcare professional who can confirm the diagnosis and previous treatments received by the participant.
* Participants capable of producing sperm must use a condom during the trial and for 12 weeks after their final dose of trial medication, if their partner is a person of childbearing potential. In addition, their partner of childbearing potential must use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) from first dosing until 12 weeks following final dosing.
* Participants of childbearing potential who have a partner capable of producing sperm must agree to use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) 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.
* Female participants who were capable of producing eggs (ova) must be postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Postmenopausal is defined as spontaneous amenorrhea for at least 12 months, and a serum follicle-stimulating hormone level in the menopausal range, unless the participant is taking hormone replacement therapy or is using hormonal contraception.
* Participant has 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, attention deficit hyperactivity disorder, current or previous history of bipolar disorder, or current borderline personality disorder.
* 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 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 antidepressant, mirtazapine, trazodone, moclobemide, buspirone, ketamine or S-ketamine, or an antipsychotic or mood stabilizer for MDD.
* 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 4 times over the participant's lifetime or any psychedelic use within 12 months prior to Screening.
* Clinically relevant history of abnormal physical health interfering with the trial as determined by medical history and physical examinations obtained during Screening as judged by the Investigator (including but not limited to, neurological, cardiovascular, respiratory, gastrointestinal \[including dyspepsia or gastroesophageal reflux disease\], hepatic, or renal disorder).
* Participants with renal insufficiency.
* Has hypothyroidism or hyperthyroidism, unless controlled on appropriate medication with no change in dosage for at least 12 weeks prior to Screening.
* Current diagnosis of uncontrolled hypertension or an arrhythmia, or clinically relevant abnormal results for heart rate or blood pressure
* History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the trial medication.
* Participant has a presence or relevant history of organic brain disorders (e.g., epilepsy, seizure, intracranial hypertension, intracranial bleed and aneurysmal disease, brain tumor or other medical conditions associated with seizures or convulsions).
* Known sensitivity to psilocin and/or any excipients present in the formulation.
* Participant is taking or has taken OTC doses of 5 hydroxytryptophan or St John's Wort within 45 days prior to trial medication administration.
* Strenuous exercise within 48 hours prior to each clinic visit.
* The participant has participated in a clinical trial and has received a medication or a new chemical entity within 12 weeks prior to dosing of current trial medication.
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cybin IRL Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Development

Role: STUDY_CHAIR

Cybin IRL Limited

Locations

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Scottsdale Research Institute

Phoenix, Arizona, United States

Site Status RECRUITING

Mountain Clinical Trials

Phoenix, Arizona, United States

Site Status NOT_YET_RECRUITING

Noble Clinical Research

Tucson, Arizona, United States

Site Status RECRUITING

Del Sol Research Management

Tucson, Arizona, United States

Site Status RECRUITING

CenExel CIT (Clinical Innovations, Inc)

Bellflower, California, United States

Site Status RECRUITING

Kadima Neuropsychiatry Institute

La Jolla, California, United States

Site Status RECRUITING

Bespoke Treatment/Lipov Medical Group

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

Catalina Research Institute

Montclair, California, United States

Site Status RECRUITING

Excell Research, Inc

Oceanside, California, United States

Site Status RECRUITING

Open Mind Collective/UCSF Medical Center Mount Zion

San Francisco, California, United States

Site Status RECRUITING

Inland Psychiatric Medical Group Inc

San Juan Capistrano, California, United States

Site Status RECRUITING

Mountain View Clinical Research

Denver, Colorado, United States

Site Status RECRUITING

Starlight Clinical Research

Evergreen, Colorado, United States

Site Status RECRUITING

Research Centers of America

Hollywood, Florida, United States

Site Status RECRUITING

K2 Medical Research-Maitland

Maitland, Florida, United States

Site Status RECRUITING

Floridian Neuroscience Institute

Miami, Florida, United States

Site Status RECRUITING

Innovative Clinical Research, INC

North Miami, Florida, United States

Site Status RECRUITING

Clinical Neuroscience Solutions, Inc

Orlando, Florida, United States

Site Status RECRUITING

Charter Research

Orlando, Florida, United States

Site Status NOT_YET_RECRUITING

Combined Research Orlando Phase I-IV

Orlando, Florida, United States

Site Status NOT_YET_RECRUITING

K2 Medical Research-Tampa

Tampa, Florida, United States

Site Status RECRUITING

Atlanta Center for Medical Research, CenExel

Atlanta, Georgia, United States

Site Status RECRUITING

CenExel iResearch Atlanta

Decatur, Georgia, United States

Site Status RECRUITING

CenExel iResearch Savannah

Savannah, Georgia, United States

Site Status RECRUITING

Great Lakes Clinical Trials, DBA Flourish Research

Chicago, Illinois, United States

Site Status RECRUITING

Uptown Research Institute

Chicago, Illinois, United States

Site Status RECRUITING

Psychiatric Medicine Associates, LLC

Skokie, Illinois, United States

Site Status RECRUITING

DelRicht Research

New Orleans, Louisiana, United States

Site Status RECRUITING

Sunstone Medical, PC

Rockville, Maryland, United States

Site Status RECRUITING

Adams Clinical Boston

Boston, Massachusetts, United States

Site Status RECRUITING

Adams Clinical

Boston, Massachusetts, United States

Site Status RECRUITING

Elixia Health

Springfield, Massachusetts, United States

Site Status RECRUITING

Redbird Research, LLC

Las Vegas, Nevada, United States

Site Status NOT_YET_RECRUITING

Oasis Clinical Trials

Las Vegas, Nevada, United States

Site Status RECRUITING

Global Medical Institues, Princeton Medical Institute

Princeton, New Jersey, United States

Site Status RECRUITING

Adams Clinical Harlem

New York, New York, United States

Site Status RECRUITING

Adams Clinical Bronx

The Bronx, New York, United States

Site Status RECRUITING

Monroe Biomedical Research

Monroe, North Carolina, United States

Site Status RECRUITING

Neurobehavioral Clinical Research

North Canton, Ohio, United States

Site Status RECRUITING

Clinical Neuroscience Solutions, CNS Healthcare

Memphis, Tennessee, United States

Site Status RECRUITING

InSite Clinical Research, LLC

DeSota, Texas, United States

Site Status RECRUITING

Zillan Clinical Research

Houston, Texas, United States

Site Status RECRUITING

AIM Trials

Plano, Texas, United States

Site Status RECRUITING

Cedar Clinical Research

Murray, Utah, United States

Site Status RECRUITING

Inner Space Research, LLC

Orem, Utah, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Clinical Development

Role: CONTACT

Phone: 877-361-4003

Email: [email protected]

Facility Contacts

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Stephen Adams

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Danielle Recasens

Role: primary

Julia Salmon

Role: primary

Role: primary

Amber Tannahill

Role: primary

Morgan Hecker

Role: primary

Katherine Prowse

Role: backup

Role: primary

Jennifer Rhode

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Tiana Tangulu

Role: primary

Tera Wolf

Role: backup

Related Links

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Other Identifiers

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CYB003-002

Identifier Type: -

Identifier Source: org_study_id