Topic starter
A new publication in the Journal of Affective Disorders, by a research team led by Carlton Kelly and Trisha Suppes, presents further findings from an open-label pilot study into psilocybin among US veterans with severe treatment-resistant depression (TRD).
Previous publications from the same trial had already reported an average reduction of 23 points on the MADRS depression scale after 3 weeks, with response rates ranging from 60% in week 3 to 80% after 6 months.
This new analysis looks beyond depression alone and examines the effects on anxiety, quality of life, functioning and PTSD symptoms.
Study design
Participants were given a a single dose of 25 mg of psilocybin (COMP360, COMPASS Pathways’ patented pharmaceutical formulation) administered in capsule form, in a supervised clinical setting with psychological support before, during and after the session.
The primary assessment took place 3 weeks after administration, with long-term follow-up up to 12 months.
The following were measured: anxiety (GAD-7), quality of life (Q-LES-Q-SF), functional impairment (WSAS) and PTSD symptoms (PCL-5), supplemented by questionnaires on the subjective experience itself: mystical experience (MEQ), challenging experience (CEQ-30) and emotional breakthrough (EBI).
A total of 15 veterans took part, 10 of whom completed the full long-term follow-up. The group consisted predominantly of men (87%) with an average age of 43.2 years, and 73% also had self-reported PTSD.
Anxiety decreased significantly and over the long term
The GAD-7 anxiety scores showed a sustainable improvement which persisted for up to 12 months after the session, with a reduction in 59% compared with baseline in week 3.
This is striking because, in treatment-resistant depression, anxiety symptoms often prove to be more persistent than the depressive symptoms themselves.
Quality of life and functioning
The quality-of-life score (Q-LES-Q-SF) rose significantly up to and including week 12, with an increase of 24% in week 3.
Functional impairment (WSAS) also improved significantly, with a reduction of 46% in week 3, and this effect persisted until the end of month 6 before it began to wane again.
Important note: after adjusting for the concurrent improvement in depression scores, these effects on quality of life and functioning were no longer statistically significant. This suggests that the improvement in quality of life and daily functioning is largely "driven" by the improvement in the depression itself.
PTSD symptoms and the role of the experience itself
For the PCL-5 (PTSD symptoms), uncorrected decreases were observed at all measurement points, which is a significant finding given the high proportion of veterans with comorbid PTSD (73%).
It is striking that the exploratory analyses of the acute subjective experience during the session itself, so however mystical, difficult or emotionally life-changing the trip was experienced to be, did not correlate with the degree of response to treatment.
In other words: however "intense" or "spiritual" a person’s experience of the session itself was, this study found that it said nothing about how much benefit they ultimately derived from it.
Conclusion
This pilot study provides preliminary evidence that psilocybin, combined with psychological support, may help to improve anxiety, quality of life and functioning in veterans with treatment-resistant depression.
Most participants experienced a substantial reduction in symptoms at an early stage, particularly in relation to anxiety, although these effects appear to be largely linked to the simultaneous improvement in depression.
The effects on PTSD symptoms were encouraging, but the authors emphasise that these findings need to be replicated in larger studies.
Addition
With only 15 participants and an open-label design (i.e. without a placebo control and without blinding), this study is small and has methodological limitations, a point which the authors themselves explicitly acknowledge.
Nevertheless, the finding is that the subjective intensity of the trip not predicted how much benefit someone would derive from it – which is remarkable, as this runs counter to a widely held assumption within the psychedelic community that "the deeper the experience, the greater the healing".
For veterans in particular, it is important to note that anxiety and PTSD symptoms are often at least as debilitating as the depression itself, and that this study shows that a well-supervised psilocybin session can provide relief in all these areas simultaneously, even though it is not yet possible to distinguish between the underlying mechanisms (whether the anxiety is improved by the substance itself or by the overall improvement in mood).
The study was funded by COMPASS Pathways, the manufacturer of the psilocybin preparation used, and several authors report financial ties to the company.
Posted : 13 September 2026 10:24