Tests psilocybin with trazodone for hard-to-treat depression
Tests psilocybin combined with trazodone in adults with treatment-resistant depression.
Key facts
- Who runs it
- Centre Hospitalier St Anne
- Where
- Paris, FranceSee the site
- Trial code
- Registry title
- Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ)
- Status
- Recruiting
- Phase
- Phase 2
- People taking part
- 112 people, planned
- Started
- 30 Jun 2026
- Expected to end
- 30 Jun 2030
- Type of study
- Interventional, 4 groupsOne group gets a placebo (a dummy treatment), for comparison.
- Treatments tested
- Psilocybin 25 mg per os
- Trazodone 5mg
- Trazodone 30 mg
- Placebo of psilocybin
- Placebo of trazodone
- Record updated
- 21 September 2026
Who can take part
AI summary
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with major depression that has not improved after at least two antidepressant medicines. It tests psilocybin together with trazodone or placebo.
- Age
- 18 years or older
- Sex
- All sexes can join
- Disease stage
- Major depressive episode without psychotic features, resistant to treatment, with a MADRS score of 20 or more
- Earlier treatment
- Did not respond to at least two antidepressant medicines at an adequate dose for 6 weeks
Main reasons for not taking part
- Bipolar disorder, schizophrenia or psychosis, or a personal or family history of psychotic disorder
- Significant suicide risk
- Alcohol or substance use disorder in the past 12 months
- Pregnancy or breastfeeding
- Heart disease, epilepsy, or uncontrolled diabetes or thyroid disorder
The registry criteria, word for word
Show all 32 criteriaShow less
Who can take part
- Patient with major depressive episode without psychotic features according to DSM-5 criteria
- 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)
- MADRS ≥ 20
- Written signed informed consent
- Patient covered by the social security system
Who cannot take part
- Patient with a psychiatric decompensation following a previous use of psychedelic substance like LSD; Comorbidities or somatic specificities:
- Contraindications to MRI; Concomitant therapies:
- Treatment with buprenorphine or opioids, clonidine, methyldopa, digoxin, Monoamine oxidase inhibitors (MAOI), aldehyde dehydrogenase (ALDH) inhibitors and alcohol dehydrogenase (ADH) inhibitors, St. John's Wort, or warfarin should be discontinued completely before study drug administration
- Use of electroconvulsive therapy and/or transcranial magnetic stimulation, during the current depressive episode; or lifetime vagus nerve stimulation, deep brain stimulation, and/or ablative neurosurgery
- Psychiatric comorbidities known from medical history or identified during inclusion assessment:
- Bipolar disorder
- Personal or family history of psychotic disorder
- History of personality disorder
- Post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders
- Alcohol or substance use disorder in past 12 months or positive urine toxins at time of assessment
- Uncontrolled diabetes
- Uncontrolled thyroid disorder
- Epilepsy
- Parkinson's disease treated by selegiline or levodopa
- HIV treated by ritonavir and indinavir
- Active infection treated by erythromycin
- Fungal infection treated by ketoconazole and itraconazole
- Persons deprived of their liberty by judicial or administrative decision, persons under compulsory psychiatric care
- Cardiovascular history (myocardial infarction, stroke, heart rhythm disorder, uncontrolled hypertension, QT interval prolongation, tachycardia and poor cardiovascular health)
- Schizophrenia and psychosis
- 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
- Pregnancy and breastfeeding women
- 5-HT antagonist treatment2A (including quetiapine, olanzapine, aripiprazole)
- Lithium treatment
- Use of psychedelics (psilocybin, lysergic acid, ayahuasca, mescaline and derivatives) during current episode; Legal status:
- Persons under legal protection or unable to give consent; 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
Where in France
- GHU Paris Psychiatrie and NeurosciencesParis, FranceContact: Lucie BERKOVITCH, MDTaking people
About the trial
What the trial wants to find out
Psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improves depressive symptoms while inducing profound acute subjective effects.
Read full original descriptionShow less
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.
The 4 groups in the trial
- Group 1Treatment being tested
Psilocybin PEX010 25 mg + trazodone placebo (pharmaceutical master preparation prepared according to GPP)
Treatment: Psilocybin 25 mg per os and Placebo of trazodone
- Group 2Treatment being tested
Psilocybin PEX010 (25 mg) + trazodone 5 mg
Treatment: Psilocybin 25 mg per os and Trazodone 5mg
- Group 3Treatment being tested
Psilocybin PEX010 (25 mg) + trazodone 30 mg
Treatment: Psilocybin 25 mg per os and Trazodone 30 mg
- Group 4Placebo, for comparison
PCB2 (Placebo of PEX010 (25)) + trazodone 30 mg
Treatment: Trazodone 30 mg and Placebo of psilocybin
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorData and sources
- Registry record
- Listed on ClinicalTrials.gov.
- Official title
- Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ)
- Plain-language title
- Tests psilocybin with trazodone for hard-to-treat depressionGenerated from the registry record. The registry title is the official one.
- AI summary
- From the trial's eligibility criteria. Read by machine on 12 November 2026.
- Record updated
- 21 September 2026