BPL-003
Darko Vlahović, D. Vlahovic
Archives of Psychiatry Research December 29, 2025 DOI: 10.20471/dec.2025.61.03.09 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 193 |
| Population | Patients with treatment-resistant depression |
| Dose | 8 mg and 12 mg |
| Duration | Single dose, with follow-up through Day 57 |
| Measures | Montgomery–Åsberg Depression Rating Scale |
| Topics | Neuroplasticity Serotonin |
| Keywords | Adverse effect Antidepressant Depression economics Clinical trial Pharmacology Anesthesia |
| Key findings | Single doses of 8 mg and 12 mg BPL-003 produced rapid and sustained reductions in depressive symptoms in patients with treatment-resistant depression, with the 8 mg dose showing a favorable efficacy-tolerability balance. |
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.
Comparable studies
Other randomized controlled trials on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased global integration in the brain after psilocybin therapy for depression. Patients with treatment-resistant depression and patients with major depressive disorder | 2022 | Open-label trial and double-blind phase II randomized controlled trial | |
| Cognitive-Affective Neural Plasticity following Active-Controlled Mindfulness Intervention Healthy human subjects | 2012 | Randomized controlled trial | |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
| Effective connectivity changes in LSD-induced altered states of consciousness in humans. Healthy participants | 2019 | Double-blind, randomized, placebo-controlled, cross-over study | n = 25 |
| Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin. | 2019 | Observational study with placebo session |