A phase 2 uncontrolled, open-label study of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine) in treatment-resistant depression

Intranasal BPL-003, a formulation of 5-methoxy-N,N-dimethyltryptamine, was tested for safety and clinical effects in patients with treatment-resistant depression. Twelve participants with moderate-to-severe major depressive disorder and treatment-resistant depression took a single 10 mg intranasal dose in a 12-week phase 2a, uncontrolled open-label design. Safety outcomes included treatment-emergent adverse events and clinical evaluations, including a readiness for discharge measure. Results reported completion by all participants and a majority experiencing treatment-related adverse events, most commonly nausea and nasal discomfort. Depression severity measured with MADRS showed a mean reduction from baseline across timepoints through Day 85, with most participants classified as responders and several in remission at least once after dosing. The study concludes the safety profile in this population is supported and that rapid, sustained symptom reductions warrant larger controlled trials.