RecruitingPhase 3NCT06793397

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

An Efficacy and Safety, Phase III, Multi-center, Double-Blind, Randomized Controlled Study Comparing 2 Active Doses of CYB003 and Placebo in Eligible Participants With Major Depressive Disorder


Sponsor

Cybin IRL Limited

Enrollment

330 participants

Start Date

Dec 10, 2025

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 85 Years

Inclusion Criteria12

  • Participants must meet all the following criteria to be included in the trial:
  • Age18 to 85 years.
  • Participant has a diagnosis of MDD.
  • Moderate to severe depression at Screening.
  • Participants have been on a stable dose of antidepressant medication at an adequate dose in the last 4 weeks prior to Screening.
  • Participant has a body mass index (BMI) of 40 kg/m2 or less (BMI ≤40 kg/m2), inclusive, at Screening.
  • Participants with well controlled hypertension.
  • Participant is able to refrain from smoking during the dosing session.
  • Participants must use a condom plus spermicide during the trial and for 12 weeks afterwards.
  • Participants of childbearing potential must agree to use a highly effective method of and 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 Criteria18

  • Participants with any of the following characteristics/conditions will be excluded from trial participation:
  • Current or previously diagnosed schizophrenia spectrum or other psychotic disorders.
  • Family history of schizophrenia, schizoaffective disorder, or bipolar disorder type 1 (first-degree relatives).
  • Significant suicide risk within 12 months of Screening.
  • Current or previous diagnosis of treatment-resistant MDD.
  • 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.
  • 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 hydroxytryptophan or St John's Wort within prior to trial medication administration.
  • Strenuous exercise prior to each clinic visit.
  • 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.

Interventions

DRUGCYB003

CYB003 is a deuterated psilocin analog.

BEHAVIORALPsychological Support

Manualized psychological support performed by facilitator.


Locations(67)

UAB Psychiatry and Behavioral Neurology

Birmingham, Alabama, United States

Lighthouse Psychiatry

Gilbert, Arizona, United States

Pillar Clinical Research - Little Rock

Little Rock, Arkansas, United States

Behavioral Research Specialists, LLC

Glendale, California, United States

Sun Valley Research Center

Imperial, California, United States

CalNeuro Research Group

Los Angeles, California, United States

ATP Clinical Research

Orange, California, United States

NRC Research Institute

Orange, California, United States

Inland Psychiatric Medical Group Inc (IPMG Research)

San Juan Capistrano, California, United States

Psychedelic Science Institute

Santa Monica, California, United States

Stanford University

Stanford, California, United States

Yale School of Medicine - Yale Program for Psychedelic Science

New Haven, Connecticut, United States

CNS Healthcare

Jacksonville, Florida, United States

Accel Research Sites - Maitland

Maitland, Florida, United States

Aqualane Clinical Research

Naples, Florida, United States

Emory University Dept of Psychiatry and Behavioral Studies

Atlanta, Georgia, United States

Psych Atlanta

Marietta, Georgia, United States

Rush University

Chicago, Illinois, United States

Tandem Clinical Research

Marrero, Louisiana, United States

Johns Hopkins Medicine

Baltimore, Maryland, United States

Institute for Integrative Therapies

Eden Prairie, Minnesota, United States

Bio Behavioral Health

Toms River, New Jersey, United States

New York State Psychiatric Institute

New York, New York, United States

SP Research PLLC

Oklahoma City, Oklahoma, United States

Adams Clinical Philadelphia

Philadelphia, Pennsylvania, United States

Flourish Research Philadelphia

Philadelphia, Pennsylvania, United States

Austin Clinical Trial Partners

Austin, Texas, United States

North Texas Clinical Trials

Fort Worth, Texas, United States

Brain Health Consultants and TMS Center

Houston, Texas, United States

Flourish Research San Antonio

San Antonio, Texas, United States

Core Clinical Research

Everett, Washington, United States

Seattle Neuropsychiatric Treatment Center

Seattle, Washington, United States

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Thompson Brain & Mind Healthcare (TBMH)

Maroochydore, Queensland, Australia

Ramsay Clinic

Melbourne, Victoria, Australia

Neurocentrix Research

Melbourne, Victoria, Australia

Monash University - Notting Hill

Notting Hill, Victoria, Australia

Institute of neuropsychiatric Care (INEP)

Prague, Czechia

Psyon s.r.o.

Prague, Czechia

A-SHINE s.r.o.

Předměstí, Czechia

Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes

Homburg, Saarland, Germany

Charité Universitaetsmedizin Berlin

Berlin, Germany

University Hospital Frankfurt

Frankfurt am Main, Germany

Central Institute of Mental Health

Mannheim, Germany

Eginitio Hospital

Athens, Greece

Attikon University Hospital

Athens, Greece

Papageorgiou General Hospital

Thessaloniki, Greece

Sheaf House - Tallaght Adult Mental Health Service

Dublin, Ireland

La Nua Day Hospital Mental Health Centre

Galway, Ireland

Uniwersytecki Szpital Kliniczny W Białymstoku

Bialystok, Poland

Promente - Centrum Neurologii i Psychogeriatrii w Bydgoszczy

Bydgoszcz, Poland

UCK

Gdansk, Poland

Centrum Badan Klinicznych PI-House Sp. z o.o

Gdansk, Poland

MTZ Clinical Research Powered by Pratia

Warsaw, Poland

Department of Pharmacology and Physiology of CNS

Warsaw, Poland

Cambridge University Hospital NHS

Cambridge, United Kingdom

Clerkenwell Health - Doncaster

Doncaster, United Kingdom

NHS Research Scotland

Edinburgh, United Kingdom

Queen Elizabeth University Hospital

Glasgow, United Kingdom

St Pancras Clinical Research

London, United Kingdom

King's College London

London, United Kingdom

Clerkenwell Health - Welbeck Street

London, United Kingdom

Re:Cognition Health

London, United Kingdom

Clerkenwell Health - Baker Street

London, United Kingdom

Wolfson Unit - Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

Ascend Clinical Research

Reading, United Kingdom

Sheffield Health and Social Care NHS Foundation Trust

Sheffield, United Kingdom

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NCT06793397


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