Clinical TrialAnxiety DisordersDMTDMTActive not recruiting

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

This double-blind, active-controlled study (n=36) aims to evaluate the preliminary clinical efficacy, safety, tolerability, and pharmacokinetics of CYB004 (DMT) in participants diagnosed with Generalized Anxiety Disorder (GAD) with depressive symptoms.

Target Enrollment
36 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

Proof-of-concept, randomised, double-blind, parallel-group Phase II study evaluating CYB004, a deuterated DMT analog, for treatment of GAD with depressive symptoms; estimated n=36.

Participants receive EMBARK manualised psychotherapy throughout; drug arms compare a full therapeutic dose versus a low (active comparator) dose given in two medicine sessions approximately three weeks apart.

Outcomes include safety, tolerability, pharmacokinetics, and preliminary clinical efficacy measures collected at acute and follow-up timepoints.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

maps

Study Arms & Interventions

Full dose

experimental

Full dose CYB004 in 2 medicine sessions (≈3 weeks apart) plus EMBARK psychotherapy.

Interventions

  • DMT
    • two sessions• 2 doses total

    Full dose CYB004; exact dose per protocol

  • Compound

    EMBARK manualised psychotherapy provided throughout study

Low dose

active comparator

Low (active comparator) dose CYB004 in 2 medicine sessions (≈3 weeks apart) plus EMBARK psychotherapy.

Interventions

  • DMT
    • two sessions• 2 doses total

    Low dose CYB004 (active comparator); exact dose per protocol

  • Compound

    EMBARK manualised psychotherapy provided throughout study

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 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.

Exclusion Criteria

  • Exclusion Criteria:
  • 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.
  • Is taking a prescription medicine (except for stable chronic dose of antidepressant/anxiolytic medication(s), sedatives/hypnotics, and hormonal contraceptives or hormonal replacement medications, if applicable), certain herbal supplements (to be reviewed by the Investigator), or over-the-counter (OTC) medicine during the 28 days before dosing.
  • Is taking or has taken over the counter (OTC) doses of 5-hydroxytryptophan or St John's Wort within 28 days prior to receiving the study drug.
  • Donation of blood or plasma of >400 mL within 1 month prior to first dosing until 4 weeks after final dosing.
  • For participants capable of producing sperm: Is not willing to abstain from sperm donation between first dosing and 3 months after final dosing.
  • For participants capable: Is pregnant, breastfeeding or planning to conceive.
  • Not fluent in the English language.
  • 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 the study drug), as judged by the Investigator.

Study Details

  • Status
    Active not recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment36 participants
  • Timeline
    Start: 2024-05-01
    End: 2025-02-28
  • Compounds
    DMTDMT
  • Topic
    Anxiety Disorders

Locations

Research Centers of America — Hollywood, Florida, United States
Innovative Clinical Research, Inc. — Miami Lakes, Florida, United States
CenExel ACMR — Atlanta, Georgia, United States
iResearch Atlanta — Decatur, Georgia, United States
Uptown Research Institute — Chicago, Illinois, United States
Cedar Clinical Research — Murray, Utah, United States

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