Psilocybin for TRD — a patient-perspective guide to navigating the evidence

Definition of TRD for trial purposes: typically means failing at least two adequate trials of different antidepressant classes. Some trials require 3-4 failed medications. This is different from the clinical definition, which varies. When screening for trials, be prepared to document your medication history: drug name, dose, duration, reason for stopping.

Trial enrollment is genuinely possible for many people who think it isn't. The Hopkins trial, COMPASS Phase 3, Usona Institute — all have enrollment criteria that are less restrictive than many people assume. Key exclusions to check: bipolar I (usually excluded), psychosis history (excluded), active suicidality (often excluded), lithium use (interaction risk). Conditions that don't exclude you: most SSRIs/SNRIs (with washout), anxiety, PTSD comorbidity.

The COMPASS Phase 3 trial (COMP360) is the most important currently active trial for TRD. Phase 3 is the final stage before FDA approval — if it succeeds, psilocybin becomes an approved medicine. Enrollment is happening at sites across the US and internationally. You can find sites at clinicaltrials.gov (NCT05624268). Participation is free and you receive psilocybin-assisted treatment at no cost.

Outside trials: Oregon service centers are legal and accessible. The experience will not have the same medical oversight as a trial, but legitimate service centers include preparation and integration support. Cost is the significant barrier ($1,000-2,500 typically). For people who have already failed multiple treatments, this cost calculation looks different than it does for someone exploring psilocybin without a treatment-resistant condition.