Psilocybin is a compound found in some mushrooms that can alter perception and mood. This study is for adults with Major Depressive Disorder (MDD). MDD is a condition where people feel very sad and lose interest in things they used to enjoy. The study will have around 240 participants who will take a single dose of either 25 mg or 5 mg of Psilocybin, or a placebo (a pill with no active medicine). The aim is to see if Psilocybin helps improve depression symptoms. Participants will be in a pleasant room with trained staff for safety and support. After the first 6 weeks, there will be a follow-up for one year to check on health and symptoms. If needed, participants may get another Psilocybin dose. To join, you must be at least 18 years old and meet specific health criteria. Some people cannot join, like those with heart or brain conditions, or who are pregnant. This study might be a chance to try a new treatment, but it's important to consider the time commitment and eligibility.

• Study lasts over a year with regular follow-ups.
• Participants receive one dose, with a chance for another during the year.
• Must meet health criteria to join; some conditions make you ineligible.