Actively Recruiting
A Phase III, Placebo-Controlled, Randomized, Double-Blind Trial of Oral Doses of CYB003 to Assess Combined Safety and Efficacy in Humans With Major Depressive Disorder
Led by Cybin IRL Limited · Updated on 2026-05-06
220
Participants Needed
46
Research Sites
4 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, tolerability, and effectiveness of CYB003, a deuterated psilocin analog, compared to a matching placebo as an additional treatment for people with Major Depressive Disorder (MDD). The study focuses on adults aged 18 to 85 who have moderate to severe depression and have not responded adequately to a stable antidepressant medication. This phase III trial aims to add knowledge about treating MDD by assessing CYB003 alongside current antidepressants and psychological support. Participants are randomly assigned to one of two groups. One group receives 16 mg of CYB003 in two dosing sessions spaced about three weeks apart, while the other group receives a placebo on the same schedule. All participants continue their current antidepressant treatments and receive manualized psychological support throughout the study. Those who do not respond to placebo may join a later extension trial to receive CYB003. Throughout the trial, participants undergo several assessments, including the Montgomery-Åsberg Depression Rating Scale (MADRS) at multiple time points from screening to 42 days after treatment begins. Other evaluations include the Beck Depression Inventory, Clinical Global Impression Scale, Generalized Anxiety Disorder scale, and Quality of Life questionnaire. Participants are monitored for safety, treatment response, and tolerability, with the total study period lasting around six weeks after dosing begins.
CONDITIONS
Brief Title
"A Study of a Deuterated Psilocin Analog (CYB003) in Humans With Major Depressive Disorder"
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Aged 18 to 85 years inclusive, at Screening
- Diagnosis of Major Depressive Disorder (single or recurrent episode) as defined by DSM-5 TR
- Depression of moderate to severe degree at Screening and Baseline
- Stable dose of a single antidepressant medication for at least one month prior to Screening with inadequate response (less than 50% improvement)
- Body mass index (BMI) of 40 kg/m2 or less at Screening
- Able to refrain from nicotine use during dosing sessions (up to 8 hours)
- Registered with a healthcare professional confirming diagnosis and previous treatments
- Participants capable of producing sperm must use condom plus spermicide during the trial and for 12 weeks after final dose
- Participants of childbearing potential must use highly effective contraception plus condom and spermicide during the trial and for 12 weeks after final dose
- Negative pregnancy test at Screening and Day 1 prior to dosing
- Female participants capable of producing eggs must use contraception unless postmenopausal or permanently sterile
- Provided written informed consent including compliance with trial requirements
You will not qualify if you...
- Current or previous diagnosis of schizophrenia spectrum or other psychotic disorders, bipolar disorder, or borderline personality disorder
- ADHD diagnosis if currently taking medication for ADHD
- Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1 in first degree relatives
- Significant suicide risk within past 6 months or suicidal behaviors within 12 months of Screening
- Treatment-resistant MDD defined as failure to respond to 2 or more antidepressants of different classes
- Electroconvulsive treatment, transcranial magnetic stimulation, deep brain stimulation, or vagal nerve stimulation in last 6 months
- Current use of monoamine oxidase inhibitors, tricyclic antidepressants, mirtazapine, trazodone, moclobemide, buspirone, ketamine or S-ketamine, antipsychotics or mood stabilizers for MDD
- More than 10 lifetime uses or recent use (within 12 months) of psychedelics or 5-HT2a receptor agonists
- Ketamine or S-ketamine use within 6 months prior to Screening
- Clinically relevant abnormal physical health interfering with the trial
- Renal insufficiency
- Uncontrolled thyroid conditions unless medicated
- Uncontrolled hypertension, arrhythmia, or abnormal heart rate/blood pressure
- Conditions interfering with trial medication absorption or metabolism
- History of organic brain disorders related to seizures
- Known sensitivity to psilocin or trial medication excipients
- Use of 5-HTP or St John's Wort within 14 days prior to trial medication
- Participation in another drug trial with medication within 12 weeks prior to dosing
- Participants capable of producing sperm unwilling to abstain from sperm donation during and 12 weeks after dosing
- Pregnant, breastfeeding, planning to conceive, or unwilling to abstain from egg donation during and 12 weeks after dosing
- History of serotonin syndrome
- Unwilling to consent to audio and video recording during sessions
- Staff or family members of Cybin IRL Limited or related organizations
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 6 weeks
Participants receive two dosing sessions of either CYB003 or placebo approximately three weeks apart, while continuing their current antidepressant medication and receiving psychological support throughout the study.
1 baseline visit and multiple follow-up visits on Days 2, 10, 21, 23, 31, and 42
Trial Site Locations
Total: 46 locations
1
Scottsdale Research Institute
Phoenix, Arizona, United States, 85022
Actively Recruiting
2
Mountain Clinical Trials
Phoenix, Arizona, United States, 85050
Actively Recruiting
3
Noble Clinical Research
Tucson, Arizona, United States, 85704
Actively Recruiting
4
Del Sol Research Management
Tucson, Arizona, United States, 85715
Actively Recruiting
5
CenExel CIT (Clinical Innovations, Inc)
Bellflower, California, United States, 90706
Actively Recruiting
6
Kadima Neuropsychiatry Institute
La Jolla, California, United States, 92037
Actively Recruiting
7
Bespoke Treatment/Lipov Medical Group
Los Angeles, California, United States, 90025
Actively Recruiting
8
Catalina Research Institute
Montclair, California, United States, 91763
Actively Recruiting
9
Excell Research, Inc
Oceanside, California, United States, 92056
Actively Recruiting
10
Open Mind Therapeutics
San Francisco, California, United States, 94114
Actively Recruiting
11
Inland Psychiatric Medical Group Inc
San Juan Capistrano, California, United States, 92675
Actively Recruiting
12
Mountain View Clinical Research
Denver, Colorado, United States, 80209
Actively Recruiting
13
Starlight Clinical Research
Evergreen, Colorado, United States, 80439
Actively Recruiting
14
Research Centers of America
Hollywood, Florida, United States, 33024
Actively Recruiting
15
K2 Medical Research-Maitland
Maitland, Florida, United States, 32751
Actively Recruiting
16
Floridian Neuroscience Institute
Miami, Florida, United States, 33135
Actively Recruiting
17
Segal Trials West Broward
North Miami, Florida, United States, 33161
Actively Recruiting
18
Clinical Neuroscience Solutions, Inc
Orlando, Florida, United States, 32801
Actively Recruiting
19
Charter Research
Orlando, Florida, United States, 32803
Actively Recruiting
20
Combined Research Orlando Phase I-IV
Orlando, Florida, United States, 32807
Actively Recruiting
21
K2 Medical Research - Tampa
Tampa, Florida, United States, 33634
Actively Recruiting
22
Atlanta Center for Medical Research, CenExel
Atlanta, Georgia, United States, 30331
Actively Recruiting
23
CenExel iResearch Atlanta
Decatur, Georgia, United States, 30330
Actively Recruiting
24
CenExel iResearch Savannah
Savannah, Georgia, United States, 31405
Actively Recruiting
25
Great Lakes Clinical Trials, DBA Flourish Research
Chicago, Illinois, United States, 60640
Actively Recruiting
26
Uptown Research Institute
Chicago, Illinois, United States, 60640
Actively Recruiting
27
Psychiatric Medicine Associates, LLC
Skokie, Illinois, United States, 60076
Actively Recruiting
28
Atlas Psychiatric
New Orleans, Louisiana, United States, 70115
Not Yet Recruiting
29
DelRicht Research
New Orleans, Louisiana, United States, 70115
Actively Recruiting
30
Sunstone Medical, PC
Rockville, Maryland, United States, 20850
Actively Recruiting
31
Adams Clinical Boston
Boston, Massachusetts, United States, 02116
Actively Recruiting
32
Adams Clinical
Boston, Massachusetts, United States, 02472
Actively Recruiting
33
Elixia Health
Springfield, Massachusetts, United States, 01103
Actively Recruiting
34
Redbird Research, LLC
Las Vegas, Nevada, United States, 89119
Actively Recruiting
35
Oasis Clinical Trials
Las Vegas, Nevada, United States, 89121
Terminated
36
Global Medical Institutes, Princeton Medical Institute
Princeton, New Jersey, United States, 08540
Actively Recruiting
37
Adams Clinical Harlem
New York, New York, United States, 100029
Actively Recruiting
38
Adams Clinical Bronx
The Bronx, New York, United States, 10461
Actively Recruiting
39
Monroe Biomedical Research
Monroe, North Carolina, United States, 28112
Actively Recruiting
40
Neurobehavioral Clinical Research
North Canton, Ohio, United States, 44720
Actively Recruiting
41
Clinical Neuroscience Solutions, CNS Healthcare
Memphis, Tennessee, United States, 38119
Actively Recruiting
42
InSite Clinical Research, LLC
DeSoto, Texas, United States, 75115
Actively Recruiting
43
Zillan Clinical Research
Houston, Texas, United States, 77433
Actively Recruiting
44
AIM Trials
Plano, Texas, United States, 75093
Withdrawn
45
Cedar Clinical Research
Murray, Utah, United States, 84107
Actively Recruiting
46
Inner Space Research, LLC
Orem, Utah, United States, 84058
Actively Recruiting
Research Team
C
Clinical Development
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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