For veterans carrying the compounded burden of treatment-resistant depression and PTSD, standard pharmacotherapy often falls short — making the durability of any intervention particularly significant. An open-label trial examining a single 25 mg psilocybin session with psychological support offers some of the longest follow-up data yet on this population, tracking outcomes well beyond the typical 4–8 week windows that dominate most psychedelic research.
Fifteen veterans with treatment-resistant depression received a single 25 mg psilocybin dose alongside structured psychological support. Anxiety severity, measured by the GAD-7, dropped 59% from baseline by week three and those gains held statistically significant through the full 12-month follow-up. Quality-of-life scores improved 24% by week three and remained significant through week 12. Functional impairment fell 46% at week three and persisted through month six before attenuating. Experiential measures — including mystical experience and emotional breakthrough scores — were correlated with depression improvements on the Montgomery-Åsberg scale. Ten of the fifteen participants completed long-term follow-up.
The anxiety finding is the most clinically interesting piece here. Most psilocybin trials have focused narrowly on depressive symptom reduction, yet anxiety and functional disability are often the metrics that most directly affect quality of life in this cohort. A 59% anxiety reduction sustained at 12 months from a single dose is a notable signal, but the sample size of 15 — with only 10 completing long-term follow-up — means every effect size must be treated as hypothesis-generating, not confirmatory. The open-label design introduces expectancy bias, and the veteran population, while critically underserved, limits generalizability. Still, the durability pattern here aligns with emerging mechanistic theories around psilocybin's effects on cognitive flexibility and fear extinction — both highly relevant to PTSD comorbidity. This qualifies as an incremental but directionally important contribution to a field still assembling its evidence base.
