The patient undergoes an initial assessment to confirm eligibility for the study. This includes a clinical evaluation to verify a diagnosis of moderate or severe depression without psychotic features, confirmed by a MINI interview and QIDS score.

The patient must have a history of not responding to at least two different antidepressant treatments, be between 25 and 60 years old, and be in good physical health without unstable medical conditions.

The patient provides informed consent to participate in the study. This involves understanding the study’s purpose, procedures, and potential risks.

The patient is prepared for the study, which includes ensuring they can speak and understand French easily and are available for a 6-month follow-up period.

Baseline measurements are taken, including brain activity using fMRI in specific regions involved in effort assessment, such as the basolateral amygdala and dorsal anterior cingulate cortex.

Depression scores are recorded using the Quick Inventory of Depressive Symptomatology (QIDS) and other relevant scales.

The patient receives a dose of psilocybin in the form of a capsule for oral use. The specific dosage and frequency are determined by the study protocol.

The administration session is monitored, and the patient’s experience is evaluated using the 5-Dimensional Altered States of Consciousness Questionnaire.

Following the administration of psilocybin, the patient undergoes further assessments to measure changes in brain activity and depression scores.

These assessments occur at multiple time points: 4 days, 1 month, and 3 months after treatment.

The patient participates in follow-up evaluations to assess the long-term effects of the treatment on depression symptoms and overall satisfaction with the therapy.

The study collects data on any adverse events or tolerance issues reported by the patient during the follow-up period.