By Pam Conboy
Part 3 (a. & b.) of this series will provide an overview of the current status of psilocybin research in a variety of conditions. Today’s article will focus on its efficacy in depression, anxiety, and trauma.
Breakthrough Therapy (2018;2019)
FDA Recognizes Psilocybin’s Therapeutic Potential in the Treatment of Depression
As mentioned in Part 1 of this series, the Food & Drug Administration (FDA), the very same institution that classified psilocybin as a Schedule I drug, also designated it as Breakthrough Therapy for treatment-resistant depression (2018) and major depressive disorder (2019). These designations served to open the floodgates to funding and research to explore its therapeutic value in mood disorders.
What started out as preclinical research has moved from small pilot studies to larger randomized trials and multi-site programs in just the last few years. Most of these human clinical trials pair one or two supervised, macrodose psilocybin sessions with a psychotherapeutic support series designed to enhance integration and assess the durability of the intervention. Although additional, larger-scale studies will validate these findings, the rapid antidepressant and anxiolytic effects of psilocybin present a very optimistic picture. Although not all encompassing, the review offered today does provide insight into the work that has been published just since 2023, as well as some of the trials presently underway.
Therapeutic Psilocybin in Depression
Large randomized trials published and synthesized since 2023 show clinically meaningful reductions in depressive symptoms after supported psilocybin use.
In one randomized, placebo-controlled, 6-week trial published in the Journal of the American Medical Association (JAMA), a 25-mg dose of (single molecule) psilocybin with psychological support was administered to 51 study participants, while 53 participants received an active control (niacin). The psilocybin intervention was associated with a rapid and sustained antidepressant effect compared with the placebo, measured as a change in depressive symptom scores. The researchers concluded that psilocybin treatment was associated with a clinically significant and sustained reduction in depressive symptoms and functional disability.
In a 2023 Psychiatry Research review and meta-analysis, investigators analyzed nine high-quality studies representing nearly 600 participating individuals. Although study designs and cohort sizes varied, their findings demonstrated a robust overall decrease in depressive symptoms following psilocybin administration.
In another systematic review and meta-analysis published in 2025, researchers analyzed 6 randomized, controlled clinical trials representing 427 study participants, comparing psilocybin to alternative depression therapies. Despite the heterogeneity of studies reviewed, the investigators concluded that the antidepressant effects of psilocybin with supportive psychotherapy are superior to comparator interventions with continuous response through the furthest 6-week follow-up.
Notably, there have been even more recent studies demonstrating that the antidepressant activity of psilocybin is incredibly durable. In a 2025 article in Cancer, researchers published a 2-year follow-up of patients who received a single dose of psilocybin combined with psychological support in a community cancer setting. Their findings demonstrated robust antidepressant activity, suggesting a potentially paradigm-changing alternative to traditional antidepressants.
Moreover, in September 2025, the Journal of Psychedelic Studies published a 5-year follow-up of a 24-person study evaluating the impact of a single dose of psilocybin in major depressive disorder. The researchers found significant and sustained reductions in depression, with a 67% complete remission at five years post-treatment. Anxiety and functional impairment were improved with self-reported positive changes in mindset, emotional health, and relationships. The study participants also reported enhanced empathy, self-acceptance, and improved interpersonal relationships.
Therapeutic Psilocybin in Anxiety
Anxiety relief has been one of the most consistent early findings of psilocybin research, with particular emphasis on the kind of existential dread associated with life-threatening diagnoses (e.g., cancer).
In a 2024 Cochrane Database Systematic Review, investigators analyzed six clinical trials representing 146 individuals diagnosed with a life-threatening disease. Their conclusions included:
- Psychedelic‐assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in anxiety when compared to an active placebo
- Psychedelic‐assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in depression when compared to an active placebo
- Psychedelic‐assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in demoralization (one of the most common measures of existential distress) compared to an active placebo
Notably, at Setas Seminary, we offer the opportunity to complete validated surveys before and 2-3 months following supported psilocybin use, using both macrodose and microdose protocols. Although we have consistently seen impressive decreases in depressive symptoms using the Hamilton Depression (HAM-D) Rating Scale, the more compelling data comes from the Generalized Anxiety 7 (GAD-7) Item Scale. Despite our limited sample size presently, quite literally, we have found that those who initially score with “severe anxiety” fall into the lowest category of “minimal anxiety” even months removed from psilocybin use.
Therapeutic Psilocybin in Trauma
Although MDMA is the most studied psychedelic in the treatment of post-traumatic disorders, psilocybin holds a great deal of therapeutic promise as well. For a deep dive into therapeutic psychedelics for PTSD, the 2023 paper, The Psychedelic Future of Post-Traumatic Stress Disorder Treatment, published in Current Neuropharmacology, is a robust resource.
An exploration of the key mechanisms that are likely to play a role in effectively processing and releasing trauma with the use of psilocybin can also be found in the 2025 Journal of Pharmacology and Experimental Therapeutics paper, Evaluating the Potential for Psilocybin as a Treatment for Post-Traumatic Stress Disorder.
Anecdotally, I can share that my partner and I have seen many deeply traumatized people who have come to Setas Seminary in search of relief. It is our experience that with the proper preparation, journey support, and integrative practices, chronic traumatic stress can be released and sustained, and positive life changes are absolutely possible. We see it all the time!
Despite the present lack of significant, placebo-controlled trials evaluating the efficacy of psilocybin for PTSD, studies are underway. These trials, as well as others for the treatment of mood disorders, are outlined in the next section.
Clinical Trials Currently Underway
Our present Psychedelic Renaissance is operating at full throttle. To emphasize the point, I have included herein a number of the most promising, active studies looking at psilocybin efficacy in depression, anxiety, and trauma.
All of these and others can be located on the Clinical Trials website.
NCT06731621 – Recruiting
NCT06455293 – Recruiting
Psilocybin Therapy for Depression in Parkinson’s Disease
NCT06303739 – Recruiting
Psilocybin-Assisted Therapy in Treatment-Resistant Depression
NCT06378229 – Recruiting
Psilocybin for Hospitalized Patients with Treatment-resistant Depression
NCT05399498 – Active, not recruiting
Psilocybin in Co-Occurring Major Depressive Disorder and Borderline Personality Disorder
NCT05554094 – Active, not recruiting
Psilocybin for the Treatment of Veterans With Post-Traumatic Stress Disorder
NCT06386003 – Not yet recruiting
Psilocybin-Assisted Cognitive Processing Therapy for Chronic PTSD
NCT06888128 – Recruiting
Coming Up
Next month, in Part 3b of this series, I’ll dive into the existing and in-process research evaluating the use of psilocybin in both neurocognitive disorders (e.g., Alzheimer’s Disease, Parkinson’s Disease, Traumatic Brain Injury, Stroke, etc), attention deficit disorders, and addiction, including alcohol, tobacco, opiates, and other substances. Virtually all of us are affected by these diseases, and psilocybin offers real hope for both symptom relief, behavioral change, and quality of life.
Pam Conboy has an undergraduate degree in biology and began her career in medical technology (clinical laboratory). A certified IIN health coach, she is currently completing a non-US-accredited doctoral degree in naturopathic medicine. Pam has worked most of her career in medical marketing in both conventional and integrative channels.
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