A Study of a N, N-dimethyltryptamine (DMT) Analog (CYB004) in Participants With Generalized Anxiety Disorder (GAD)

NCT06051721 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: CYB004-002
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this proof-of-concept trial is to examine the safety, tolerability, and pharmacokinetics (PK), and preliminary clinical efficacy of CYB004 participants with GAD.

Conditions

Generalized Anxiety Disorder

Keywords

Generalized Anxiety Disorder; GAD; Depression; CYB004; CYB004-002; Psychedelic; DMT; N, N-dimethyltryptamine

Outcome Measures

Primary Outcomes (1)

• Hamilton Anxiety Rating Scale (HAM-A)

  The HAM-A is a 14-item scale that is used to rate the severity of symptoms of anxiety. Each of the 14 items is defined by a series of symptoms and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Items are scored from 0 (not present) to 4 (very severe), for a total score ranging from 0 to 56. Scores \<17 indicate mild anxiety, scores of 18 to 24 indicate mild to moderate anxiety, and scores of 25 to 30 or higher indicate moderate to severe anxiety.

  Screening (Day-63 and Day-1), Day 2, Day 8, Day 21, Day 23, Day 29, Day 43, Day 64, Day 85, Day 169, Day 266, and End of Treatment (Day 364)

Secondary Outcomes (1)

• Hamilton Depression Scale (HAM-D)

  Screening (Day-63 and Day-1), Day 2, Day 8, Day 21, Day 23, Day 29, Day 43, Day 64, Day 85, Day 169, Day 266, and End of Treatment (Day 364)

Study Arms (2)

Arm A: Active

EXPERIMENTAL

Arm A participants will receive a full dose of CYB004 in 2 of 2 medicine sessions, approximately three weeks apart. All participants will receive supportive EMBARK psychotherapy throughout the study.

Drug: CYB004; Behavioral: Psychotherapy

Arm B: Control

ACTIVE COMPARATOR

Arm B participants will receive a low dose of CYB004 in 2 of 2 medicine sessions, approximately three weeks apart. All participants will receive supportive EMBARK psychotherapy throughout the study.

Drug: CYB004; Behavioral: Psychotherapy

Interventions

CYB004 DRUG

CYB004 is a synthetic deuterated N, N-Dimethyltryptamine (DMT) analog.

Arm A: Active; Arm B: Control

Psychotherapy BEHAVIORAL

Manualized psychotherapy (called EMBARK) performed by facilitators

Arm A: Active; Arm B: Control

Eligibility Criteria

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

You may qualify if:

• Aged between 18 to 65 years, inclusive, at Screening.
• Has a diagnosis of GAD (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition \[DSM-V\] of moderate to severe degree), established through a full psychiatric work up.
• Has a BMI of 18 to 40.0 kg/m2, inclusive at Screening.
• Has been on a stable dose of antidepressant/anxiolytic medication (no more than 50% change) in the last month prior to Screening and has had an inadequate response, as judged by the Investigator.
• Is willing to refrain from taking any benzodiazepines for 5 days or buspirone (or other 5-HT1A agonist) during the 24 hours preceding each dosing visit.
• Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• Has a primary DSM-5 psychiatric diagnosis other than GAD within the past 6 months established through a full psychiatric work-up. A secondary diagnosis of MDD may be permissible.
• Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder, brief psychotic disorder or borderline personality disorder; current or previous history of psychosis or bipolar disorder.
• Currently taking a monoamine oxidase inhibitor, tricyclic antidepressant, trazadone, mirtazapine, or a mood stabilizer (including lithium) or has taken any of these medications in the last 3 weeks of trial participation.
• Currently taking antipsychotic medication which are 5-HT2 antagonists or has taken such medication in the last 3 weeks of trial participation.
• Clinically significant risk of suicidality, as determined through a comprehensive psychiatric interview.
• 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, hepatic, or renal disorder).
• Currently receiving treatment for hypertension or arrhythmia.
• Clinically relevant abnormal laboratory results.
• 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 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 trial, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this trial.
• Has a presence or relevant history of any 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).
• 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.
• 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 and Day 22.
• Has participated in a clinical trial and has received a medication or a new chemical entity within 3 months prior to dosing of current study medication.
• Known sensitivity to DMT or ayahuasca.

Sponsors & Collaborators

• Cybin IRL Limited: lead
• Worldwide Clinical Trials: collaborator

Study Sites (6)

Research Centers of America

Hollywood, Florida, 33024, United States

Location

Innovative Clinical Research, Inc.

Miami Lakes, Florida, 33016, United States

Location

CenExel ACMR

Atlanta, Georgia, 30331, United States

Location

iResearch Atlanta

Decatur, Georgia, 30330, United States

Location

Uptown Research Institute

Chicago, Illinois, 60640, United States

Location

Cedar Clinical Research

Murray, Utah, 84107, United States

Location

MeSH Terms

Conditions

Generalized Anxiety Disorder; Depression

Interventions

Psychotherapy

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Study Officials

• Amir Inamdar, MBBS, DNB, MFPM

  Cybin IRL Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 25, 2023
• Study Start: May 10, 2024
• Primary Completion: October 14, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 27, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)