BPL-003

A single intranasal dose of the investigational psychedelic BPL-003 (5-MeO-DMT) rapidly reduced depressive symptoms in a Phase 2b randomized controlled trial of 193 patients with treatment-resistant depression. The 8 mg and 12 mg doses produced statistically significant improvements on the Montgomery–Åsberg Depression Rating Scale as early as Day 2, sustained through Day 57. The 8 mg dose offered the best balance between efficacy and tolerability. Adverse effects were transient and mild. BPL-003 acts preferentially at 5-HT1A receptors and induces neuroplastic changes in frontal cortical regions, supporting its potential as a fast-acting, single-dose therapy for treatment-resistant depression.

Study at a glance

Abstract

BPL-003 is a novel investigational psychedelic compound being developed for the treatment-resistant depression (TRD). Its active ingredient, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), is a serotonergic psychedelic with preferential agonism at 5-HT1A receptors and rapid pharmacokinetics, allowing for a brief, supervised in-clinic administration. Preclinical studies demonstrate that 5-MeO-DMT induces robust neuroplastic effects, including increased dendritic spine formation in frontal cortical regions. Early clinical studies showed rapid onset of antidepressant effects following a single intranasal dose. In a Phase 2b randomized, controlled trial involving 193 patients with TRD, single doses of 8 mg and 12 mg BPL-003 produced rapid and statistically significant reductions in depressive symptoms as measured by the Montgomery–Åsberg Depression Rating Scale. Clinical improvement was evident as early as Day 2 and was sustained through Day 57, with the 8 mg dose demonstrating a favorable balance between efficacy and tolerability. BPL-003 was generally well tolerated, with transient and mild adverse effects that resolved within the observation period. These findings position BPL-003 as a promising fast-acting, single-dose therapeutic option for TRD and support further evaluation in Phase 3 clinical trials.