Clinical TrialTreatment-Resistant Depression (TRD)5-MeO-DMTPlacebo5-MeO-DMTCompleted

A Trial of GH001 in Patients With Treatment-resistant Depression

Randomised, double-blind, placebo-controlled Phase 2b trial (n=81) testing inhaled GH001 (5‑MeO‑DMT) individualized dosing regimen (IDR) vs placebo in patients with treatment‑resistant depression.

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

Detailed Description

This Phase 2b trial randomises patients with treatment‑resistant depression 1:1 to a single‑day individualized inhalation dosing regimen (IDR) of GH001 (5‑MeO‑DMT; up to 3 escalating doses: 6, 12, 18 mg) or placebo in a double‑blind parallel design; primary endpoint is change in MADRS at Day 7.

Patients completing the 7‑day double‑blind part may enter a 6‑month open‑label extension during which they may receive up to five GH001 IDRs as clinically indicated; safety, mood, anxiety and quality‑of‑life measures are assessed across both parts.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

GH001 (DB)

experimental

Individualised dosing regimen (IDR) inhalation on a single day with up to 3 escalating doses (6, 12, 18 mg); DB Part 1 experimental arm.

Interventions

  • 5-MeO-DMT6 - 18 mg
    via Inhalation• single day IDR• 3 doses total

    Up to 3 escalating doses (6→12→18 mg) on single clinic day; later doses only if no peak experience.

Placebo (DB)

inactive

Placebo IDR inhalation on a single day, matched to GH001 IDR.

Interventions

  • Placebo
    via Inhalation• single day IDR• 3 doses total

    Placebo IDR with up to 3 administrations matched to GH001 schedule.

Open-label extension

experimental

OLE Part 2: single-arm open-label GH001; patients may receive up to five GH001 IDRs over 6 months.

Interventions

  • 5-MeO-DMT6 - 18 mg
    via Inhalation• up to 5 IDRs over 6 months• 5 doses total

    Up to 5 IDRs as needed during 6-month OLE; IDR dosing same as DB part.

Participants

Ages
18 – 64
Sexes
Male & Female

Inclusion Criteria

  • Main Inclusion Criteria:
  • 1. Is in the age range between 18 and 64 years (inclusive) at the time of informed consent;
  • 2. Meets the trial criteria for TRD as assessed by a study psychiatrist:
  • 1. 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;
  • 2. 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;
  • 3. Had nonresponse (≤25% improvement) to ≥2 and ≤5 oral antidepressant treatments administered during the current episode of depression.

Exclusion Criteria

  • Main Exclusion Criteria:
  • 1. 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;
  • 2. Has significant suicide risk;
  • 3. 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;
  • 4. Undergoing systematic psychotherapy that is planned to be modified or planning to initiate psychotherapy during the trial;
  • 5. 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;
  • 6. 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;
  • 7. 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;
  • 8. 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.

Study Details

Locations

Investigational site — Pilsen, Czechia
Investigational site — Prague, Czechia
Investigational Site — Dresden, Germany
Investigational Site — Frankfurt, Germany
Investigational Site — Münster, Germany
Investigational site — Dublin, Ireland
Investigational Site — Galway, Ireland
Investigational Site — Maastricht, Netherlands
Investigational Site — Gdansk, Poland
Investigational Site — Barcelona, Spain
Investigational Site — Salamanca, Spain

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