**BPL-003 Efficacy and Safety in Treatment Resistant Depression Study** This study is for people with treatment-resistant depression (TRD), which means they haven't felt better after trying at least two different medicines. TRD patients will receive a single dose of BPL-003 through the nose. This study is **randomized** (participants don't choose their dose), **quadruple masked** (neither participants nor doctors know who gets which dose), and takes place at multiple locations. Psychological support will be provided before, during, and after treatment. **Key Points:** - **Timeline**: The study lasts 8 weeks with follow-up check-ins. - **Participation**: About 225 people will be involved, receiving either a low, medium, or high dose. - **Eligibility**: Participants must have moderate or severe depression and may need to stop their current antidepressant. Before joining, make sure you don't have conditions like schizophrenia, bipolar disorder, or uncontrolled medical issues. Also, women and men must agree to use contraception. If you have a seizure history or a serious medical condition, check with the study team to see if you qualify.