Additional Study Information: We are currently enrolling adult individuals with treatment-resistant depression (TRD) for this research study. This study is investigating a new treatment approach for people with TRD using an investigational medicine (psilocybin) given with psychological support. Psilocybin is the active ingredient in some forms of psychedelic mushrooms and its effects can include euphoria, visual hallucinations, changes in perception, a distorted sense of time, and spiritual experiences. This study is suitable for people who are currently experiencing a recurrent or single episode of depression, but who have not responded to antidepressant treatment. The study may last up to 16 weeks and study visits will include physical examination, vital signs, electrocardiograms, blood collection, urine collection, and psychological assessments. Participants will be divided into two groups and randomly (by chance, like the flip of a coin) allocated to receive either psilocybin or placebo. Neither the participants nor the study staff will be told which treatment, psilocybin or placebo, participants received.