**Study on Treatment Resistant Depression** This study is for people with treatment resistant depression (**TRD**), which means their depression hasn't improved with at least two different treatments. The study will test a nasal spray medication called **BPL-003** to see if it helps. There will be about 225 participants who will receive one dose of BPL-003 and have follow-up appointments for 8 weeks to check how they are doing. Participants will also get psychological support during this time to help them feel better. To join, you must have at least moderate depression and be willing to stop any current antidepressant medications. You cannot participate if you have a history of certain mental health disorders like schizophrenia or bipolar disorder, or if you've had issues with drugs or alcohol. Pregnant women or those not willing to use contraception cannot join. **Key Points**: - The study involves one dose of medication and lasts for 8 weeks. - Participants will receive psychological support throughout the study. - Certain health conditions or histories will make you ineligible to join.