In an open-label trial, 20 patients with treatment-resistant depression described their experiences six months after psilocybin treatment. They reported two main shifts: from feeling disconnected from themselves, others, and the world to feeling connected, and from avoiding emotions to accepting them. Patients contrasted psilocybin with conventional treatments like medications and short-term talking therapies, which they said reinforced disconnection and avoidance, whereas psilocybin encouraged connection and acceptance. The findings suggest psilocybin may work through a novel mechanism opposite to standard antidepressants and some therapies.
A randomized, placebo-controlled trial is testing the feasibility of psilocybin-assisted therapy for people with major depressive disorder who have not responded to at least two prior treatments. Up to 60 participants in London, UK receive either 25 mg psilocybin or a placebo in a single dosing session, along with psychological therapy. The primary outcomes are recruitment rates, dropout rates, and variance in depression scores measured by the Montgomery Asberg Depression Rating Scale at 3 and 6 weeks. The trial also collects neuroimaging and omics data and offers an open-label extension dose of psilocybin.