RecruitingPhase 2

A Mechanistic Study to Assess a Single Dose of CYB003 in Participants With Depression and Anxiety

A Randomized, Double-Blind, Placebo-Controlled Mechanistic Study to Assess a Single Oral Dose of CYB003 in Participants With Major Depressive Disorder (MDD) and Moderate to Severe Anxiety

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
21 Years to 65 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Questionnaires, Interviews, MRI scans, Blood draws

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Assessments include interviews, self-report questionnaires, EEG and fMRI to measure symptoms and brain function."
  • "The study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity assessed using electroencephalography (EEG)/electromyography (EMG) and functional magnetic resonance imaging (fMRI)/ diffusion-weighted magnetic resonance imaging (DWI) after administration of one oral dose of CYB003."
  • "Assessments performed at Baseline and on Day 2 and Day 21 after administration will include EEG/EMG, MRI, clinician (MADRS, HAM-A, C-SSRS) scales and self-report questionnaires to assess depression and anxiety symptoms, cognitive testing, self-report questionnaires to evaluate the psychedelic effects of CYB003 administration, and blood draw of the Gsα-AC biomarker assay."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests how one dose of CYB003, a drug related to psilocybin, may help depression and anxiety. It is for adults ages 21–65 with major depression and moderate to severe depression and anxiety symptoms. Participants receive the drug or a placebo (no active drug), then have interviews, surveys, and tests of brain activity.

The goal of this study is to learn how psychedelics may help symptoms of depression and anxiety. Participants with major depressive disorder experiencing symptoms of depression and anxiety will receive one dose of either a drug related to psilocybin or a placebo. Assessments include interviews, self-report questionnaires, EEG and fMRI to measure symptoms and brain function.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 21–65 years old and have been assigned female or male at birth.
  • Have a BMI of 18–30, a measure based on height and weight, and weigh at least 60 kg (about 132 pounds).
  • Have major depressive disorder confirmed by a study clinician.
  • Have moderate to severe symptoms: a depression score of at least 21 and an anxiety score of at least 10 on the study’s rating scales.
  • Have depression that has not improved enough with your current antidepressant. Take an SSRI or SNRI antidepressant with no dose change greater than 50% in the month before screening.
  • Follow the study’s condom and highly effective birth control rules during the study and for 3 months after the dose if you or your partner could become pregnant.
  • If you could become pregnant, have negative pregnancy tests at screening and Day 1. If you no longer can, meet the study’s rules for menopause or surgery that prevents pregnancy.
  • Sign a consent form and agree to follow the study rules.

Who can't join

  • Your depression score drops by at least 25% between screening and the starting visit, or more than 2 properly tried antidepressant treatments have failed during your current depression episode.
  • You have a past or current psychotic disorder, which can affect your sense of reality, or bipolar disorder; a current personality disorder; or a parent, sibling, or child with schizophrenia, schizoaffective disorder, or type 1 bipolar disorder.
  • The study team finds a serious suicide risk, including certain suicidal thoughts in the past 6 months or any past suicidal behavior.
  • You had a substance use disorder in the past year, drink more than 21 alcohol units weekly, or cannot follow the study’s alcohol limits. Psychedelic use within 6 months, or more than 10 times in 10 years, also rules you out.
  • You take medicines that are not allowed, including antidepressants other than SSRIs or SNRIs, antipsychotics, or mood stabilizers. Other medicines and supplements affecting the brain or interacting with psilocybin need study team review.
  • You have a health problem that could make the study unsafe or affect results, including certain brain disorders, seizures, high blood pressure, an irregular heartbeat, low thyroid function, or problems with how your body handles the drug.
  • You have important abnormal findings on blood, urine, heart, or other screening tests. The listing also says 'positive urine test' but does not state what the test checks.
  • You are not fluent in English, or the study team finds another health or personal issue that could prevent safe participation.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: * Participant is assigned female or male at birth. * Participant is aged between 21 to 65 years, inclusive, at Screening. * Participant has a BMI of 18 to 30 kg/m2, inclusive, at Screening. * Participant is ≥60 kg. * Participant has a diagnosis of MDD (as defined in the DSM-5 established through a clinician interview that includes the Mini-International Neuropsychiatric Interview) * Depression severity moderate to severe based on MADRS score ≥21. * Anxiety severity moderate to severe based on GAD-7 ≥10. * Inadequate response to current antidepressant medication in current episode of depression. * Participant has been on a stable dose (no more than 50% change) of antidepressant medication (SSRI or SNRI) in the last month prior to Screening. * Participants capable of producing sperm must use a condom during the trial and for 3 months after their 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 dosing until 3 months following dosing. * Participants of childbearing potential 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 use of a condom by a partner who is capable of producing sperm, during the trial and for 3 months after dosing. Such participants must have a negative pregnancy test at Screening and Day 1. * Participants of non-childbearing potential who are or were capable of producing eggs (ova) must be postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy or bilateral oophorectomy. Postmenopausal is defined as spontaneous amenorrhea for at least 12 months, and a serum follicle stimulating hormone (FSH) level in the menopausal range, unless the participant is taking hormone replacement therapy or is using hormonal contraception. * Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Exclusion Criteria: * A reduction in the MADRS score of 25% or more between Screening and Baseline. * Failure to respond to \>2 antidepressant treatments given at an adequate dose for an adequate duration during the current episode of depression. * Current or previously diagnosis of schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder or brief psychotic disorder; current or previous history of bipolar disorder, or current personality disorder (as determined by MINI at Screening). * Clinically significant risk of suicidality, as determined through a comprehensive psychiatric interview that incorporates the Columbia Suicide Severity Rating Scale (CSSRS); a score of 4 or higher on the suicidal ideation subscale of C-SSRS (past 6 months) or any suicidal behaviour (lifetime), would be exclusionary. * History of substance use disorder within the 12 months, as assessed by a structured clinical interview (Mini International Neuropsychiatric Interview \[MINI\], Version 7.0.2) or determined by self-report, or intake of \>21 units of alcohol weekly, and the inability to refrain from alcohol use from 48 hours before Screening and each scheduled visit until discharge from the study site. One unit is equivalent to a 285 mL glass of full-strength beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine. * Currently receiving a monoamine oxidase inhibitor, tricyclic antidepressant, other non-SSRI or non-SNRI antidepressants (e.g. bupropion, mirtazapine, etc), an antipsychotic or a mood stabilizer. * Exposure to psilocin, or any other psychedelics, such as ayahuasca, mescaline, LSD or peyote more than 10 times in the last 10 years, or any psychedelic use within 6 months prior to Screening. * Use of psychotropic medicine/supplement (or medicine/supplement that would interact with psilocybin) during the 28 days before dosing. Participants may take a stable chronic dose of antidepressant medication(s) and/or sedatives/hypnotics. The Investigator and study team may review medication on a case-by-case basis to determine if its use would compromise participant safety or interfere with study procedures or data interpretation. * Family history of schizophrenia or schizoaffective disorder (first degree relatives), or bipolar disorder type 1 (first degree relatives). * Clinically relevant history of abnormal physical health interfering with the study as determined by medical history and physical examinations obtained during Screening as judged by the Investigator (including but not limited to, neurological, endocrine, cardiovascular, respiratory, gastrointestinal \[including dyspepsia or gastroesophageal reflux disease\], hepatic, or renal disorder). * Participant has a presence or relevant history of any of the following medical conditions: 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). * Diagnosis of hypertension or arrhythmia. * Clinically relevant abnormal heart rate (resting supine heart rate \>100 bpm) or blood pressure (resting supine systolic blood pressure (SBP) above 140 mmHg or diastolic blood pressure (DBP) above 90 mmHg) at screening. Screening supine SBP, DBP and heart rate for evaluation will be the average of 3 readings obtained after at least 5 minutes rest. Participants with abnormal vital signs which are out of range and deemed clinically significant by the Investigator at Day 1, following triplicate readings. * Presence of clinically significant ECG abnormalities at the Screening visit, as defined by medical judgement. * QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 msec at Screening, following triplicate ECG readings. * Hypothyroidism and/or current abnormal thyroid function tests. In case of uncertain or questionable screening thyroid function test results, the TSH test may be repeated once during screening. The TSH test must be reviewed to ensure that it is within normal limits before randomizing a participant into the study. * Clinically relevant abnormal laboratory results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis), 12-lead ECG and vital signs, or physical findings at Screening. In case of uncertain or questionable results, tests performed during Screening may be repeated once to confirm eligibility or judged to be clinically irrelevant. * Other eligibility considerations (i.e., participant personal circumstances, behavior, and/or any current problem that might interfere with participation or that is incompatible with establishment of rapport or safe exposure to psilocin), as judged by the Investigator. * 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 (ADME) of the study drug. * Any other concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study as outlined in this Protocol, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study. * Participant is not fluent in English. * Aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) or total bilirubin levels ≥1.5 x the upper limit of normal (ULN) at Screening. These laboratory evaluations may be repeated once at the discretion of the Investigator. If the repeat test is within the reference range, the participant may be included if the Investigator considers that the previous finding will not introduce additional risk factors. * Positive urine test for drugs of abuse or alcohol breath test at Screening or Day 1. A positive test for cannabinoids (e.g., marijuana) at Screening may not exclude a participant if after discussion with and evaluation by the Investigator, the participant agrees not to use any marijuana or other cannabinoid products during the study, and if allowed to participate, the participant must test negative for cannabinoids on Day 1. * Participant who consumes excessive amounts of caffeine (e.g., coffee, tea, caffeinated sodas) or (methyl) xanthines (e.g., chocolate) based on the Investigator's determination and discretion. * The participant has participated in a clinical study and has received a medication or a new chemical entity within 3 months prior to dosing of current study medication. * Known sensitivity to psilocin and/or any excipients present in the formulation. Known fructose malabsorption or intolerance, since the orange drink vehicle for study drug contains fructose. * Participant is taking or has taken any drugs known to inhibit monoamine oxidase within 28 days prior to study drug administration. * Participant is taking or has taken OTC doses of 5-hydroxytryptophan or St John's Wort within 28 days prior to study drug administration. * Strenuous exercise within 48 hours prior to each visit, and while at the study site. * Participants capable of producing sperm who will not abstain from sperm donation between first dosing and 3 months after final dosing. * Participants of childbearing potential who are pregnant, breastfeeding or planning to conceive.

Study sites (1)

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