This study is for adults with treatment-resistant depression (TRD), which means their depression hasn't improved after trying several treatments. The study tests the effectiveness and safety of COMP360, a new medication. Participants will be randomly assigned to receive one of three doses of COMP360: 25mg, 10mg, or 1mg. They will also get psychological support to help with their depression symptoms.

The study will last up to 16 weeks, including screening time and follow-up. To join, participants must be at least 18 years old and have major depression without psychotic features. They should have tried different treatments for depression without success. People with certain mental health conditions, like bipolar disorder or schizophrenia, cannot participate.

• The study lasts up to 16 weeks, with different treatment groups.
• Participants receive psychological support along with the medication.
• Eligibility requires a history of unsuccessful depression treatments.