Psychedelic therapy is quickly gaining recognition as a possible treatment for psychiatric illness across much of the diagnostic spectrum. This talk will focus on the early evidence for the safety and efficacy of psychedelic therapy within patients with particularly difficult to treat presentations of depression including bipolar type II depression, depression with chronic active suicidal ideation and severely treatment resistant depression. Insights will be shared from the experience of a master clinical researcher as he explored the use of psilocybin.