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

NCT06820723 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025H0027
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Depression; Anxiety; Major Depressive Disorder

Keywords

psychedelics

Outcome Measures

Primary Outcomes (4)

• Changes in parameter estimate of regional brain activity measured by fMRI after one dose of CYB003 in participants with MDD and anxiety

  Change in Blood oxygenation level dependent (BOLD) fMRI signal after task comparing CYB003 group and placebo group

  Between Baseline and Time point 24 hours and 21 days post-Investigational Product or placebo

• Changes in region-to-region connectivity measured by fMRI after one dose of CYB003 in patients with depression and anxiety

  Changes in resting state activity of brain areas comparing CYB003 group and placebo group

  Between Baseline and Time point 24 hours and 21 days post-Investigational Product or placebo

• Changes in event related potentials (ERP) after one dose of CYB003 in participants with MDD and anxiety

  Change in ERP as assessed by Electroencephalography (EEG) after task comparing CYB003 group and placebo group

  Between Baseline and Time point 24 hours and 21 days post-Investigational Product or placebo.

• Changes in acoustic startle electromyographic (EMG) response after one dose of CYB003 in patients with depression and anxiety

  Changes in acoustic startle magnitude measured by EMG after task comparing CYB003 group and placebo group

  Between Baseline and Time point 24 hours and 21 days post-Investigational Product or placebo.

Secondary Outcomes (5)

• Effect of CYB003 on depression symptoms

  Between Baseline and Time point 24 hours and 21 days post-Investigational Product administration or placebo

• Effect of CYB003 on anxiety symptoms

  Between Baseline to 24 hours and 21 days post-Investigational Product administration or placebo

• Effects of CYB003 on Patient Health Questionnaire (PHQ-9) self-report questionnaire of depression

  Between Baseline to 24 hours and 21 days post-Investigational Product administration or placebo

• Effects of CYB003 on Beck Depression Inventory (BDI) self-report questionnaire of depression

  Between Baseline to 24 hours and 21 days post-Investigational Product administration or placebo

• Effects of CYB003 on Generalized Anxiety Disorder (GAD)-7 self-report questionnaire of anxiety

  etween Baseline to 24 hours and 21 days post- Investigational Product administration

Study Arms (2)

CYB003

EXPERIMENTAL

Participants will receive one dose of CYB003

Drug: CYB003

Placebo

PLACEBO COMPARATOR

Participants will receive one dose of placebo

Drug: Placebo

Interventions

CYB003 DRUG

synthetic, deuterated isotopomer of psilocin

CYB003

Placebo DRUG

Placebo orange drink solution

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University Department of Psychiatry

Columbus, Ohio, 43210, United States

Location

Related Publications (8)

• Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.

  PMID: 27210031 RESULT

• Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.

  PMID: 33146667 RESULT

• Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Palenicek T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443.

  PMID: 36322843 RESULT

• Gorka SM, Young CB, Klumpp H, Kennedy AE, Francis J, Ajilore O, Langenecker SA, Shankman SA, Craske MG, Stein MB, Phan KL. Emotion-based brain mechanisms and predictors for SSRI and CBT treatment of anxiety and depression: a randomized trial. Neuropsychopharmacology. 2019 Aug;44(9):1639-1648. doi: 10.1038/s41386-019-0407-7. Epub 2019 May 6.

  PMID: 31060042 RESULT

• Nutt D. Psychedelic drugs-a new era in psychiatry? . Dialogues Clin Neurosci. 2019;21(2):139-147. doi: 10.31887/DCNS.2019.21.2/dnutt.

  PMID: 31636488 RESULT

• Raison CL, Sanacora G, Woolley J, Heinzerling K, Dunlop BW, Brown RT, Kakar R, Hassman M, Trivedi RP, Robison R, Gukasyan N, Nayak SM, Hu X, O'Donnell KC, Kelmendi B, Sloshower J, Penn AD, Bradley E, Kelly DF, Mletzko T, Nicholas CR, Hutson PR, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis MC, Nelson-Douthit C, Wilson S, Brown C, Linton W, Ross S, Griffiths RR. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):843-853. doi: 10.1001/jama.2023.14530.

  PMID: 37651119 RESULT

• Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165-1180. doi: 10.1177/0269881116675512.

  PMID: 27909164 RESULT

• Vollenweider FX, Kometer M. The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nat Rev Neurosci. 2010 Sep;11(9):642-51. doi: 10.1038/nrn2884. Epub 2010 Aug 18.

  PMID: 20717121 RESULT

MeSH Terms

Conditions

Depression; Anxiety Disorders; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mental Disorders; Depressive Disorder; Mood Disorders

Study Officials

• Luan Phan, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne-Marie Duchemin

CONTACT

6142935517; anne-marie.duchemin@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only the research pharmacist and nurse providing drug will be unblinded.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair, Department of Psychiatry and Behavioral Health

Model Details: Participants will be randomized to drug or placebo (1:1)

Study Record Dates

• First Submitted: January 29, 2025
• First Posted: February 11, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: October 30, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)