Clinical Research Directory

Inclusion Criteria: * 18 years or older, capable of making decisions, and able to provide informed consent. * Major Depressive Disorder (MDD) according to DSM-5 criteria * Current depressive episode of moderate to severe intensity * Episode duration of at least two weeks * Baseline MADRS score ≥ 20 * No treatment changes (including antidepressants) in the 4 weeks prior to the study * Abstain from psychedelics ≥14 days before dosing (D0) and during the 12-month follow-up Exclusion criteria: * Major cardiac, hepatic, or renal disease; unstable cardiovascular conditions * Uncontrolled hypertension, QTc prolongation, arrhythmias, or valvular disease COPD or asthma * Severe obesity, uncontrolled diabetes, coagulopathy, thyroid disease, or glaucoma * Neurological risk (e.g., aneurysm, ↑ICP, epilepsy/seizures, severe disorders) * MAO deficiency or history of serotonin syndrome * Pregnant, breastfeeding, positive test, or no effective contraception * Secondary depression * Cluster B personality disorders (incl. borderline with ≥2 suicidal behaviors in past 12 months) or poor therapeutic rapport * Psychotic disorders, MDD with psychotic features, or first-degree family history of psychosis/bipolar disorder * Mania/hypomania (YMRS ≥8) * OCD, dissociative disorders, active PTSD, or decompensated eating disorders * Moderate-severe use disorder (past 6 months; except nicotine/caffeine) * Lifetime ketamine, PCP, psychedelics, or MDMA use disorder * Current use of MAO inhibitors, unless discontinued at least 14 days prior to dosing * Psychedelic trial participation in past 12 months * Cognitive impairment affecting valid assessment