A Phase 2 interventional study of Psilocybin 25 mg per os and Trazodone 5mg in Depression - Major Depressive Disorder and Treatment-resistant Depression (TRD), sponsored by Centre Hospitalier St Anne. Recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by Centre Hospitalier St Anne · Phase 2, Interventional, and Treatment
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Among 25 studies testing psilocybin in Depressive Disorder, Treatment-Resistant — 9 open to participants now, 14 under way, 2 of them phase 3. Psilocybin · Depressive Disorder, Treatment-Resistant.
Among the 25 studies testing psilocybin in Depressive Disorder, Treatment-Resistant, this one is the 5th largest by planned enrollment, is one of 3 that started in 2026, is one of 18 in phase 2, reaches primary completion later than 11 of the 13 other live ones, and was the 22nd registered.
448 studies on the registry are indexed under Depressive Disorder, Treatment-Resistant; 147 are open to participants now.
Browse Depressive Disorder, Treatment-Resistant studies →9 of the 25 studies testing psilocybin in Depressive Disorder, Treatment-Resistant are open now, in 6 countries. Recruiting first, the newest first:
Centre for Addiction and Mental Health · Sites in Canada
Ages 18–70
Beersheva Mental Health Center · Sites in Israel
Ages 18–65
Centre for Addiction and Mental Health · Sites in Canada
Ages 18–65
University of Texas at Austin · Sites in United States
Ages 22–65
University Hospital, Ghent · Sites in Belgium
Ages 18+
By country, each count listing its studies:
No approval found in the FDA or EMA files read. How studies give it is on its page →
Of the 114 Depressive Disorder, Treatment-Resistant studies recruiting now, 26 (23%) set no upper age limit and 76 (67%) stop at 75 or younger; 1 takes children under 18; 13 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
25 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 3 · Phase 2 19 · Phase 3 3
First in 2019; this study’s year is marked. 3 started in 2026.
By drug class, each counting the studies that test any of its medicines:
This study's planned enrollment of 112 is above the median of 59 across 372 interventional studies indexed under Depressive Disorder, Treatment-Resistant.
Median enrollment 30 across the 25 interventional studies. Of the 9 that completed or were terminated, 2 (22%) have results posted.
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4 of 25 have an industry lead sponsor. The 10 most frequent:
Centre Hospitalier St Anne is the lead sponsor of 101 studies on the registry; 55 are open to participants now.
Centre Hospitalier St Anne has 3 studies filed under Depressive Disorder, Treatment-Resistant — fewer than ten, so there is no comparison to draw.
3 of the studies testing psilocybin in Depressive Disorder, Treatment-Resistant that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06731621Centre for Addiction and Mental HealthPsilocybin for Treatment-Resistant Depression in Autism | 2027-01 |
| NCT06518720Centre for Addiction and Mental HealthTreatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND) | 2027-03 |
| NCT07183748Beersheva Mental Health CenterPsilocybin Microdosing With Psychotherapy for Treatment-Resistant Depression | 2027-06-01 |
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Among the 25 studies testing psilocybin in Depressive Disorder, Treatment-Resistant, from their registry updates:
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Psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improves depressive symptoms while inducing profound acute subjective effects.
The benefit-risk ratio of psilocybin in treatment-resistant depression seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on the therapeutic efficacy of psilocybin is still poorly understood. For example, pre-administration of trazodone, a 5-HT2A antagonist antidepressant, could annihilate the acute subjective effects of psilocybin without altering its beneficial effects (Rosenblat et al., 2023). We intend to test this hypothesis by comparing, in a randomized, double-blind, placebo-controlled study, the effect of two possible doses of trazodone (total or partial occupancy of 5-HT2A receptors) on the benefit/risk ratio of psilocybin.
We hypothesize that the therapeutic effects of psilocybin are partially independent of 5-HT2A receptor activation and thus persist even after total or partial neutralization of its acute subjective effects.
Treatment-resistant depression (TRD) is a frequent and potentially severe psychiatric disorder characterized by specific neurocognitive impairments. It has previously been demonstrated that psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improved depressive symptoms while inducing profound acute subjective effects.
The benefit-risk ratio of psilocybin in TRD seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on the therapeutic efficacy of psilocybin is still poorly understood. For example, pre-administration of trazodone, a 5-HT2A antagonist antidepressant, could annihilate the acute subjective effects of psilocybin without altering its beneficial effects (Rosenblat et al., 2023). We intend to test this hypothesis in a randomized, double-blind, placebo-controlled phase II, monocentric, 4 parallel-group proof-of-concept study involving 112 adult subjects with a depressive episode who had failed to respond to at least two lines of antidepressant treatment. Patients will be randomized in a 1:1:1:1 ratio to one of the following treatment groups:
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Psychiatric comorbidities known from medical history or identified during inclusion assessment:
Comorbidities or somatic specificities:
Concomitant therapies:
Legal status:
Other:
- Any clinical manifestation which, in the opinion of the investigator, may interfere with the interpretation of study results or constitute a health risk to the participant if he or she participates in the study.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Psilocybin PEX010 25 mg + trazodone placebo (pharmaceutical master preparation prepared according to GPP)
Drug: Psilocybin 25 mg per os · Drug: Placebo of trazodone
Psilocybin PEX010 (25 mg) + trazodone 5 mg
Drug: Psilocybin 25 mg per os · Drug: Trazodone 5mg
Psilocybin PEX010 (25 mg) + trazodone 30 mg
Drug: Psilocybin 25 mg per os · Drug: Trazodone 30 mg
PCB2 (Placebo of PEX010 (25)) + trazodone 30 mg
Drug: Trazodone 30 mg · Drug: Placebo of psilocybin
Caps of psilocybin administered orally once (V3) under medical and psychologist supervision in group 1, 2, and 3 and in an open-label setting for group 4
Oral preparation of trazodone administered orally once (V3) with psilocybin in Group 2
Oral preparation of trazodone administered orally once (V3) with psilocybin in Groups 3 \& 4
Caps of psilocybin placebo will be administered at V3 in group 4
A placebo of trazodone will be administered orally at V3 in group 1
Change from Baseline in the mean score of Montgomery-Åsberg Depression Rating Scale (MADRS) at 1 month
Mean difference of MADRS scores between one month and Baseline, between the following groups: psilocybin + trazodone 30 mg (Group 3) and placebo + trazodone (Group 4).
Time frame: Baseline, Month 1
Change from Baseline in the MADRS scores at Month1 in the Groups 1, 2 and 4
MADRS scores at Baseline and Month 1 in the Groups 1, 2 and 4
Time frame: Baseline and Month 1
Change from Inclusion in the MADRS scores at Baseline, Day0 H7, Day 1, Day 7, Month 2 and Month 3 in each group
MADRS scores at Inclusion, Baseline, Day0 H7, Day 1, Day 7, Month 2 and Month 3 in each group
Time frame: Inclusion, Baseline, Day0 H7, Day 1, Day 7, Month 2 and Month 3
Change from Inclusion in the Beck Depression Inventory (BDI-II) scores at Baseline, Day0 H7, Day 1, Day 7, Month 1, Month 2 and Month 3 in each group
BDI-II scores at Inclusion, Baseline, Day0 H7, Day 1, Day 7, Month 1, Month 2 and Month 3 in each group
Time frame: Inclusion, Baseline, Day0 H7, Day 1, Day 7, Month 1, Month 2 and Month 3
Change from Inclusion in the Columbia-Suicide Severity Rating Scale (C-SSRS) scores at Baseline, Day0 H7, Day 1, Day 7, Month 1, Month 2 and Month 3 in each group
C-SSRS scores at Inclusion, Baseline, Day0 H7, Day 1, Day 7, Month 1, Month 2 and Month 3 in each group
Time frame: Inclusion, Baseline, Day0 H7, Day 1, Day 7, Month 1, Month 2 and Month 3
Response rate
Proportion of patients with 50% reduction in MADRS scores in each group at Day 7, Month 1, Month 2 and Month 3 compared to Baseline
Time frame: Baseline, Day 7, Month 1, Month 2 and Month 3
Remission rate
Remission rates defined as the proportion of patients with a MADRS score \<10 in each group at Day 7, Month 1, Month 2 and Month 3 compared to Baseline score
Time frame: Baseline, Day 7, Month 1, Month 2 and Month 3
Number of adverse events observed including vital signs and clinical laboratory abnormalities
Side effects in all groups between study drug administration at Day 0, Day 1, Day 7, Month 1, Month 2 and Month 3 including vital signs worsening and biological adverse events (laboratory exams worsening)
Time frame: Day 0, Day 1, Day 7, Month 1, Month 2, Month 3
Change from Inclusion in the mean YMRS at Baseline, Day 0 H7, Day 1, Day 7, Month 1, Month 2 and Month 3
Mean YMRS scores at Inclusion, Baseline, Day 0 H7, Day 1, Day 7, Month 1, Month 2 and Month 3 in each group
Time frame: Inclusion, Baseline, Day 0 H7, Day 1, Day 7, Month 1, Month 2, Month 3
Proportion of patients with a new antidepressant after study treatment administration (Day 0)
Proportion of patients with an introduction of a new antidepressant after Day 0 in each group
Time frame: From Day 0 to end of study
Mean score of visual analog scale (VAS) of patients' drug acute subjective effects at Day 0
Time frame: Day 0
Mean scores of Mystical Experience Questionnaire (MEQ30) at Day 0
Time frame: Day 0
Mean score of 5-Dimensional Altered States of Consciousness (5D-ASC) at Day 0
Time frame: Day 0
Mean score of Stanford Expectations of Treatment Scale (SETS) at Baseline
Time frame: Baseline
Mean score of the Credibility/Expectancy Questionnaire (CEQ) at Baseline
Time frame: Baseline
Change from Inclusion in the mean score of Quality of Life in Depression Scale (QLDS) at Baseline, Day 7, Month 1, Month 2 and Month 3
Time frame: Inclusion, Baseline, Day 7, Month 1, Month 2 and Month 3
Change in mean reaction time from Baseline at Day 0, Day 7, Month 1and Month 3
Time frame: Baseline, Day 0, Day 7, Month 1, Month 3
Plan to share: Undecided
No publications or documents are linked to this record.
Started Jun 2026 (actual). Primary completion is estimated for Dec 2029, 42 months after the start.
Of 50 phase 2 interventional studies under Depressive Disorder, Treatment-Resistant, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 41. This study's planned 42 months is above that.
How these figures are worked out, and which studies are left out of them.
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Studies of the drugs tested here: Psilocybin · Trazodone
Depressive Disorder, Treatment-Resistant →