This study aims to investigate whether oxytocin reactivity during a psychedelic session for MDD treatment predicts treatment response, specifically by examining its relationship with changes in flexibility and depressive symptoms.

Inclusion Criteria:

• Age >=18 years-old
• MDD defined by DSM-V criteria, and resistant to treatment
• Ongoing classical psychotherapeutic treatment
• Agreement to discontinue necessary psychotropic medications (some classes of anti-depressants are allowed with no need to taper off).

Exclusion Criteria:

• Psychotic or bipolar disorder
• High suicidal risk
• Severe cardiovascular, hepatic or neurological (affecting the central nervous system) disorders
• Pregnancy or breastfeeding.

Participants will be invited to participate among consecutive patients with treatment-resistant MDD enrolled for psychedelic treatment in the Division of addictology-Department of Psychiatry of the Geneva University hospitals) after receiving approval from the Swiss Federal Office of Public health for compassionate treatment with LSD or psilocybin. Only those receiving LSD or psilocybin for the first time (first treatment cycle) will be included.