The aim of this randomized, double-blind, placebo-controlled, phase 2b clinical trial is to investigate the safety and efficacy of GH001 (containing mebufotenin \[5-methoxy-N,N-dimethyltryptamine; 5-MeO-DMT\]) in patients with treatment-resistant depression (TRD). The study is comprised of a 7-day double-blind (DB) part (Part 1) and a 6-month open-label extension (OLE) part (Part 2). Patients will be randomized to receive GH001 or placebo in a 1:1 ratio. The primary endpoint is the mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to Day 7.
Who can participate
Age range
18 Years – 64 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Is in the age range between 18 and 64 years (inclusive) at the time of informed consent;
. Meets the trial criteria for TRD as assessed by a study psychiatrist:
. Meets the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria for single-episode major depressive disorder (MDD) or recurrent MDD, without psychotic features confirmed by the Mini-International Neuropsychiatric Interview (MINI) with current episode duration of ≤2 years;
. The current major depressive episode must be deemed "valid" based upon the Massachusetts General Hospital State versus trait Assessability Face and Ecological validity Rule of 3Ps (MGH SAFER) criteria interview;
. Had nonresponse (≤25% improvement) to ≥2 and ≤5 oral antidepressant treatments administered during the current episode of depression.
Exclusion criteria
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
. Has, based on history, psychiatric assessment, and evaluation of the MINI during the screening period, a first MDD episode after age 60, a current or prior diagnosis of a psychotic disorder, MDD, or other mood disorder with psychotic features, bipolar disorder, obsessive compulsive disorder, posttraumatic stress disorder, autism spectrum disorder, borderline personality disorder, schizophrenia, delusional disorder, paranoid personality disorder, schizoaffective disorder, clinically significant intellectual disability, antisocial personality disorder, schizotypal personality disorder, or any other psychiatric comorbidity that renders the patient unsuitable for the trial according to a study psychiatrist;
. Has significant suicide risk;
. Has 1 or more first degree relatives with a current or prior diagnosis of bipolar disorder, psychotic disorder, or other mood disorder (including MDD) with psychotic features;
. Undergoing systematic psychotherapy that is planned to be modified or planning to initiate psychotherapy during the trial;
. Has any current or past clinically significant condition that may interfere with the interpretation of the trial results, constitute a health risk for the patient, or that otherwise renders the patient unsuitable for the trial according to the investigator's judgement;
. Fulfils criteria for DSM-5 alcohol or substance use disorder (excluding tobacco and caffeine use disorders) within the preceding 1 year, as assessed via the MINI;
. Is taking antidepressants, antipsychotics, or any medication with monoamine oxidase inhibitors activity or takes or has taken other disallowed recent or concomitant treatments or it is anticipated that the patient will require treatment with at least 1 of the disallowed concomitant treatments during the trial;
. Has previously experienced a significant adverse reaction to a hallucinogenic or psychedelic drug (e.g., psilocybin, Psilocybe spp. mushrooms, 5-MeO-DMT, DMT, ayahuasca, lysergic acid diethylamide, mescaline) according to the investigator's judgement.