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-sberg 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
Research Team
C
Clinical Development
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