BPL-003 Efficacy and Safety in Treatment Resistant Depression is a study aiming to see how well a medicine called BPL-003 works for people whose depression doesn't get better with usual treatments. It involves 225 people who will get a single dose of BPL-003 through the nose. They will be checked for 8 weeks after getting the medicine to see how they feel. The study also includes psychological support before, during, and after the treatment. Participants need to have tried at least two other depression treatments that didn't work and should not have certain mental health issues like schizophrenia or bipolar disorder. They must also agree to stop any current depression medications. The study will not include people with certain medical conditions, recent suicidal behavior, or those with certain family mental health histories.

• The study lasts for about 8 weeks with several follow-up visits.
• Participants receive support and monitoring throughout.
• Some people will not be eligible due to health conditions or medication history.