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Evaluating the effects of COMP360 on treatment-resistant depression

A Phase III, Multicentre, Randomised, Double-blind, Controlled Study to Investigate the Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With Treatment-resistant Depression

Phase 3 Interventional COMPASS Pathways · NCT05711940

This study is testing if a new psilocybin-based treatment called COMP360 can help adults with treatment-resistant depression feel better when combined with psychological support.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment568 (estimated)
Ages18 Years and up
SexAll
SponsorCOMPASS Pathways Industry-sponsored
Locations96 sites (Bellflower, California and 95 other locations)
Trial IDNCT05711940 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial investigates the efficacy, safety, and tolerability of two doses of COMP360, a psilocybin-based treatment, in adults with treatment-resistant depression (TRD). The study will randomly assign 568 participants to receive either 25 mg, 10 mg, or 1 mg of COMP360, alongside psychological support, over a period of up to 16 weeks. Participants will be monitored for improvements in depressive symptoms using standardized assessments. The trial aims to provide insights into the potential of psilocybin as a viable treatment option for individuals who have not responded to conventional antidepressant therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of treatment-resistant depression who have not responded to multiple antidepressant treatments.

Not a fit: Patients with bipolar disorder or those who have not experienced adequate treatment resistance may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients suffering from treatment-resistant depression.

How similar studies have performed: Previous studies on psilocybin have shown promising results in treating depression, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

1. Aged ≥18 years at Screening
2. Major depression without psychotic features (single or recurrent episode as informed by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition \[DSM-5\])
3. If the current major depressive episode is the participant's first lifetime episode of depression, the length of the current episode must be ≥3 months and ≤2 years at Screening
4. MADRS total score ≥20 at Screening and Baseline to ensure at least moderate severity of depression
5. TRD, defined as failure to respond to an adequate dose and duration of two, three, or four different pharmacological treatments for the current episode as determined through the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and using the supplementary advice on additional antidepressants not included in MGH-ATRQ
6. At Screening, agreement to discontinue all prohibited medications

Key Exclusion Criteria:

1. Prior or ongoing bipolar disorder, any psychotic disorder, including schizophrenia, schizophreniform disorder, schizoaffective disorder, brief psychotic disorder (unless substance induced or due to a medical condition), antisocial personality disorder as assessed by a structured clinical interview (MINI 7.0.2)
2. Lifetime paranoid, schizoid, schizotypal, histrionic, narcissistic personality disorder, or any ongoing serious psychiatric comorbidity based on medical history and clinical judgement
3. Borderline personality disorder as demonstrated by medical history or the Mini International Neuropsychiatric Interview Plus (MINI plus) - borderline personality disorder module
4. Ongoing post-traumatic stress disorder, obsessive-compulsive disorder, or anorexia nervosa as assessed by medical history and a structured clinical interview (MINI 7.0.2)
5. Psychiatric inpatient within the past 12 months prior to Screening
6. Use of electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation during the current depressive episode
7. Transcranial magnetic stimulation within the past six months prior to Screening
8. Current enrolment in a psychological therapy programme that will not remain stable for the duration of the study. Psychological therapies cannot have been initiated within 30 days prior to Screening
9. Exposure to COMP360 psilocybin therapy prior to Screening

Where this trial is running

Bellflower, California and 95 other locations

+46 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Treatment Resistant Depressionpsilocybin
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.