This randomized clinical trial enrolled 39 adults with major depressive disorder (ages 27–65) and tested 2 mg psilocybin taken once per week. Participants were split into psilocybin-first (18 people) and placebo-first (17 people) groups for the first 4 weeks, followed by 4 weeks where everyone received psilocybin. Depression scores dropped in both groups over time, and the treatment was well tolerated with no serious adverse events, but the psilocybin group did not show significantly greater symptom reduction than placebo.