Understanding Treatment-Resistant Depression
Depression affects millions worldwide and is often treated with medications, therapy, or a combination of both. But for some, these methods fail to provide relief. When someone does not improve after trying at least two different antidepressants, their condition is called treatment-resistant depression (TRD). People with TRD usually face more severe and long-lasting symptoms that affect work, relationships, and overall quality of life.
Doctors often try multiple strategies for TRD—switching medications, combining drugs, or adding other agents like antipsychotics. Still, many patients see little progress. This is why researchers are exploring new options, including psychedelic compounds like psilocybin.
A Closer Look at Psilocybin
Psilocybin is the active compound in certain mushrooms, often referred to as “magic mushrooms.” In research settings, psilocybin is being studied as a potential treatment for depression, anxiety, PTSD, and addiction. When used in carefully controlled environments with trained therapists, psilocybin has shown the ability to produce rapid and sometimes lasting improvements.
However, psilocybin is not without risks. Some people may experience anxiety, confusion, nausea, or distressing hallucinations. In most countries, it is still considered a controlled substance, which limits its availability outside of clinical studies.
The Veteran Study
A new pilot study published in the Journal of Affective Disorders investigated the long-term effects of psilocybin for U.S. military veterans living with severe TRD. The study followed 10 veterans who received a single 25 mg capsule of psilocybin at Stanford University School of Medicine.
Before the dosing day, participants completed several preparatory therapy sessions. On dosing day, the psilocybin experience lasted between 6 to 8 hours, with two licensed therapists present for support. Afterward, participants engaged in integration sessions to help process their experiences.
Researchers assessed symptoms using standard depression and functioning scales over the course of 12 months.
Promising Results
The findings were striking. At the 6-month mark, half of the participants were in remission, meaning their depression symptoms were minimal or gone. Eighty percent had experienced a clinically meaningful reduction in symptoms.
By 9 months, the antidepressant effects began to decline, though some benefits remained. At 12 months, 40% of participants still met criteria for a positive response, and 30% were still in remission. These results suggest that psilocybin can have long-lasting effects, though its strongest impact appears within the first 6 months.
Limitations and Next Steps
Despite the positive outcomes, the study had limitations. The small sample size of only 10 participants means results cannot be generalized widely. Additionally, there was no control group, so researchers cannot rule out placebo effects or natural fluctuations in symptoms. Participants also knew they were receiving psilocybin, which could have influenced expectations and outcomes.
Still, this early evidence adds to growing research suggesting psilocybin may be a powerful tool for those who have not responded to conventional depression treatments. Future studies with larger groups, control conditions, and long-term monitoring will help clarify its full potential.
Why This Matters
Treatment-resistant depression leaves many patients without hope after traditional therapies fail. The fact that a single dose of psilocybin could provide significant relief for up to a year is both groundbreaking and encouraging. While more rigorous research is needed, this study highlights how psychedelic-assisted therapy could reshape the future of mental health care.
References
- Ellis S, Bostian C, Donnelly A, Feng W, Eisen K, Lean M, Conlan E, Ostacher M, Aaronson S, Suppes T. Long-term outcomes of single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression – 12-month data from an open-label pilot study. Journal of Affective Disorders. 2025;389:119655. doi:10.1016/j.jad.2025.119655. https://www.sciencedirect.com/science/article/abs/pii/S0165032725010973?utm_source=chatgpt.com
- Carhart-Harris, R. L., & Goodwin, G. M. (2017). The therapeutic potential of psychedelic drugs: Past, present, and future. Neuropsychopharmacology, 42(11), 2105–2113. https://www.nature.com/articles/npp201784