Open-label, ascending-dose, within-subject tolerability study (n=20) of MDMA (40, 80, 120 mg) in clinically stable patients with schizophrenia to assess psychotic symptom response at 24 hours.
Impaired social motivation (asociality) is a disabling negative symptom of schizophrenia with no effective pharmacologic treatment; MDMA has pro-social effects in healthy volunteers and other psychiatric disorders and may target social motivation deficits.
This open-label, ascending-dose, single-group trial will administer oral MDMA in ascending order (40 mg, 80 mg, 120 mg) within subjects, stopping escalation if participants exhibit moderate or greater psychotic symptoms at 24 hours.
Primary tolerability outcome is clinician-rated psychotic symptoms at 24 hours; findings will inform selection of a maximum well-tolerated dose for future efficacy studies targeting social deficits.
Within-subject ascending single doses of MDMA (40 → 80 → 120 mg) assessing tolerability.
First session 40 mg, ascending if tolerated; stop escalation if moderate+ psychotic symptoms at 24 h.
Second session 80 mg in ascending schedule.
Third session 120 mg if prior doses tolerated; primary tolerability assessed at 24 h.