DRY EXTRACT FROM PSILOCYBE CUBENSIS (15-25:1), EXTRACTION SOLVENT: METHANOL for Treatment-resistant depression

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years old"}
• {"criterion_text":"- Patient with major depressive episode without psychotic features according to DSM-5 criteria"}
• {"criterion_text":"- MADRS score ≥ 20"}
• {"criterion_text":"- Treatment-resistant depressive episode, i.e. failure to respond to at least two lines of antidepressant medication at an adequate dose and for a sufficient period of time (6 weeks according to the MGH-ATRQ)"}
• {"criterion_text":"- Free, informed and prior written consent of the patient"}
• {"criterion_text":"- Persons covered by the social security system"}

Exclusion criteria

• {"criterion_text":"- Bipolar disorder"}
• {"criterion_text":"- Uncontrolled thyroid disorder"}
• {"criterion_text":"- Significant suicide risk, as defined by: (a) suicidal ideation as indicated by items 4 or 5 on the C-SSRS within the past six months, at Screening, during the Screening Period, or at Baseline (b) demonstrating suicidal behaviors in the past six months, or; (c) clinical assessment of significant suicidal risk or risk of self-injury during participant interview"}
• {"criterion_text":"- Epilepsy"}
• {"criterion_text":"- Contraindications to MRI: Implants (mechanical or electronic: cochlear implants, pacemakers, infusion pumps, magnetic clips, etc.) incompatible with the magnetic field; Metallic foreign bodies in the eye or nervous system; Claustrophobia; Non-removable dental removable braces"}
• {"criterion_text":"- 5-HT2A antagonist treatment (including quetiapine, olanzapine, aripiprazole)"}
• {"criterion_text":"- Lithium treatment"}
• {"criterion_text":"- Treatment with buprenorphine or opioids"}
• {"criterion_text":"- Use of psychedelics (psilocybin, lysergic acid, ayahuasca, mescaline and derivatives) during current episode"}
• {"criterion_text":"- Persons deprived of their liberty by judicial or administrative decision, persons under compulsory psychiatric care"}
• {"criterion_text":"- Persons under legal protection or unable to give consent"}
• {"criterion_text":"- Any clinical event that, 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"}
• {"criterion_text":"- Schizophrenia and psychosis"}
• {"criterion_text":"- Patient with a psychiatric decompensation following a previous use of psychedelic substance like LSD"}
• {"criterion_text":"- Parkinson’s disease treated by selegiline or levodopa"}
• {"criterion_text":"- HIV treated by ritonavir and indinavir"}
• {"criterion_text":"- Active infection treated by erythromycin"}
• {"criterion_text":"- Fungal infection treated by ketoconazole and itraconazole"}
• {"criterion_text":"- Concomitant therapies"}
• {"criterion_text":"- Legal status"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Personal or family history of psychotic disorder"}
• {"criterion_text":"- History of personality disorder"}
• {"criterion_text":"- Post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders"}
• {"criterion_text":"- Alcohol or substance use disorder in past 12 months or positive urine toxins at time of assessment"}
• {"criterion_text":"- Pregnancy and breastfeeding women"}
• {"criterion_text":"- Cardiovascular history (myocardial infarction, stroke, heart rhythm disorder, uncontrolled hypertension, QT interval prolongation, tachycardia and poor cardiovascular health)"}
• {"criterion_text":"- Uncontrolled diabetes"}

Primary endpoints

• {"endpoint_text":"- The efficacy of the single administration of the psilocybin + trazodone 30 mg combination at 1 month will be assessed by the mean difference of Montgomery-Åsberg Depression Rating Scale (MADRS) scores between M1 (V6) and Baseline (V2), between the following groups: psilocybin + trazodone 30 mg (Group 3) and placebo + trazodone (Group 4).","definition_or_measurement_approach":"Mean difference in MADRS scores between M1 (V6) and Baseline (V2) comparing Group 3 (psilocybin + trazodone 30 mg) versus Group 4 (placebo + trazodone)."}

Secondary endpoints

• {"endpoint_text":"- MADRS scores at Baseline (V2) and M1 (V6) in the groups not tested in the primary endpoint (Group 1, 2 and 4)","definition_or_measurement_approach":"MADRS scores at specified visits compared across Group 1, Group 2 and Group 4."}
• {"endpoint_text":"- MADRS scores at Inclusion (V1), Baseline (V2), H7 (V3), D1 (V4), D7 (V5), M2 (V7) and M3 (V8) in each group (Group 1, 2, 3 and 4)","definition_or_measurement_approach":"Longitudinal MADRS scores at listed visits for each group."}
• {"endpoint_text":"- Beck Depression Inventory (BDI) questionnaire scores at Inclusion (V1), Baseline (V2), H7 (V3), D1 (V4), D7 (V5), M1 (V6), M2 (V7) and M3 (V8) in each group","definition_or_measurement_approach":"BDI questionnaire scores at listed timepoints for each group."}
• {"endpoint_text":"- C-SSRS scores at Inclusion (V1), Baseline (V2), H7 (V3), D1 (V4), D7 (V5), M1 (V6), M2 (V7) and M3 (V8) in each group","definition_or_measurement_approach":"Columbia-Suicide Severity Rating Scale scores at listed visits for safety and suicidal ideation/behavior assessment."}
• {"endpoint_text":"- The response rate, defined as the proportion of patients with 50% reduction in MADRS score in each group at D7 (V5), M1 (V6), M2 (V7) and M3 (V8)","definition_or_measurement_approach":"Proportion of patients achieving ≥50% reduction in MADRS at specified timepoints by group."}
• {"endpoint_text":"- The remission rate defined as the proportion of patients with remission (i.e. MADRS score <10) in each group at D7 (V5), M1 (V6), M2 (V7) and M3 (V8)","definition_or_measurement_approach":"Proportion of patients with MADRS <10 at specified visits by group."}
• {"endpoint_text":"- Side effects in all groups between study drug administration at D0 (V3), D1 (V4), D7 (V5), M1 (V6), M2 (V7) and M3 (V8) including vital signs worsening and biological adverse events (AE) (laboratory exams worsening)","definition_or_measurement_approach":"Adverse events, vital sign changes and laboratory abnormalities collected at listed visits across groups."}
• {"endpoint_text":"- YMRS scores at Inclusion (V1), Baseline (V2), H7 (V3), D1 (V4), D7 (V5), M1 (V6), M2 (V7) and M3 (V8) in each group","definition_or_measurement_approach":"Young Mania Rating Scale scores at listed visits for each group."}
• {"endpoint_text":"- Proportion of patients with an introduction of a new antidepressant after study treatment administration (D0) in each group","definition_or_measurement_approach":"Proportion of participants initiating a new antidepressant post D0, by group."}
• {"endpoint_text":"- Correlation degree between maximal 5D-ASC and Mystical Experience Questionnaire (MEQ30) scores recorded during study drug administration (D0) and therapeutic efficacy assessed by MADRS score at M1 (V6)","definition_or_measurement_approach":"Correlation analysis between peak 5D-ASC/MEQ30 during D0 and MADRS at M1."}
• {"endpoint_text":"- Stanford Expectations of Treatment Scale (SETS) score and the Credibility/Expectancy Questionnaire (CEQ) score at Baseline (V2) according to MADRS score at D7 (V5), M1 (V6), M2 (V7) and M3 (V8)","definition_or_measurement_approach":"Association of baseline SETS and CEQ with subsequent MADRS outcomes at listed visits."}
• {"endpoint_text":"- Quality of Life in Depression Scale (QLDS) score at Inclusion (V1), Baseline (V2), D7 (V5), M1 (V6), M2 (V7) and M3 (V8)","definition_or_measurement_approach":"QLDS scores measured at listed timepoints for each group."}
• {"endpoint_text":"- Cognitive task performance measured before (Baseline (V2)), during (D0 (V3)) and after study treatment administration (D7 (V5), M1 (V6) and M3 (V8)) by accuracy, reaction time and EEG signals","definition_or_measurement_approach":"Cognitive task accuracy, reaction times and EEG metrics at specified visits."}
• {"endpoint_text":"- Brain activity measured by resting EEG before (Baseline (V2)), during (D0 (V3)) and after study treatment administration (D7 (V5), M1 (V6) and M3 (V8))","definition_or_measurement_approach":"Resting EEG recordings at listed visits to assess brain activity changes."}
• {"endpoint_text":"- Immune and neuroplasticity biomarkers dosage before (Baseline (V2)) and after study treatment administration (D1 (V4), D7 (V5), M1 (V6) and M3 (V8))","definition_or_measurement_approach":"Quantification of immune and neuroplasticity biomarkers at specified timepoints."}
• {"endpoint_text":"- Independent factors and clinical response obtained during the study, defined as a 50% reduction in MADRS score","definition_or_measurement_approach":"Identification of independent predictors associated with clinical response (≥50% MADRS reduction)."}
• {"endpoint_text":"- Brain structure and activity measured by Magnetic Resonance Imaging (MRI) and EEG in the Group 4 during the open-label extension phase (if applicable). MRI + EEG will be recorded at rest and during the performance of cognitive tasks, before psilocybin administration (V2) and after administration (D7 ± 1 day (V5) and M1 ± 3 days (V6))","definition_or_measurement_approach":"MRI and EEG assessments at specified times pre- and post-psilocybin in Group 4 during open-label extension."}
• {"endpoint_text":"- MADRS scores at Baseline (V2) and M1 (V6) in the Group 4 and 4C (receiving psilocybin 25 mg in the open-label extension phase) as within-subject measures of psilocybin efficacy","definition_or_measurement_approach":"Within-subject MADRS comparisons for Group 4 vs Group 4C at Baseline and M1."}
• {"endpoint_text":"- MADRS scores at Baseline (V2) and M1 (V6) in the Group 1 and 4C (receiving psilocybin 25 mg in the open-label extension phase) as within-subject measures of efficacy and in the Group 1 and 4C to assess the influence of blindness","definition_or_measurement_approach":"Within-subject MADRS comparisons between Group 1 and Group 4C to evaluate efficacy and influence of blinding."}

France

Earliest CTIS Part Ii Submission Date

12-05-2025

Latest Decision Or Authorization Date

24-09-2025

Processing Time Days

135

Number Of Sites

1

Number Of Participants

112

Primary sponsor

Full Name

Groupe Hospitalier Universitaire Paris Psychiatrie & Neuroscience

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"ANR & DGOS","duties_or_roles":"Source of monetary support","organisation_type":""}