Psilocybin to Treat Depression in Spinal Cord Injury

This Phase I/Phase II, non-randomised, triple‑masked, sequential trial (n=30) will evaluate the safety and tolerability of oral psilocybin (5 mg, 10 mg and 25 mg) in veterans with chronic spinal cord injury and a diagnosed depressive disorder. The primary focus is to determine whether psilocybin increases the number or severity of treatment‑related adverse events (recorded in an adverse events log) over the study period, with secondary assessment of tolerability of the psychedelic experience and effects on depression severity, pain, muscle spasms, autonomic measures and quality of life. Thirty participants (15 with paraplegia and 15 with tetraplegia) will be allocated to one of three dose cohorts (low 5 mg, medium 10 mg, high 25 mg) in a stepwise safety design; participants will be masked to dose. Enrolment covers up to 13 months and includes at least 16 study visits (including seven visits comprising psilocybin‑assisted therapy), in‑person visits at the VA medical centre and remote visits, and follow‑up assessments through study completion. Key eligibility requirements include age ≥22 years, chronic spinal cord injury ≥1 year, weight ≥50 kg, ability to swallow pills and to taper antidepressants under clinician supervision; major exclusions include recent psychedelic, ketamine or ECT exposure, Bipolar I disorder, certain substance use disorders, uncontrolled hypertension and pregnancy or nursing.