# The Clinical Applications of Psilocybin Therapies and Post-COVID Syndrome: A Comprehensive Narrative Review

**Authors:** Alfred Mathew, Roshan Dongre, Seo Hee Kim, Jack Turner, Alen Mathew, Ellie Cherryholmes, Millad Mehrinfar, Sagar Kamprath

PMC · DOI: 10.7759/cureus.86659 · Cureus · 2025-06-24

## TL;DR

This review explores how psilocybin therapies may help treat mental health issues and post-COVID symptoms, highlighting their potential and current research gaps.

## Contribution

The paper provides a comprehensive review of psilocybin's clinical applications in mental health and post-COVID syndrome, emphasizing its potential and limitations.

## Key findings

- Psilocybin shows potential in treating depression, anxiety, and PTSD with relatively safe outcomes under medical supervision.
- Evidence suggests psilocybin may help with post-COVID symptoms, though more clinical trials are needed.
- Psilocybin's possible inhibition of SARS-CoV-2 protease is promising but requires in vitro validation.

## Abstract

The coronavirus variant (causing the COVID-19 disease) that led to a pandemic sent global shockwaves, resulting in long-term effects on physical, mental, and social well-being and impacting both individuals and communities. With the pandemic’s notable impact on mental health, one such potential treatment discussed in recent literature is psilocybin. Psilocybin is a naturally occurring prodrug compound found in select mushrooms shown to reduce clinical symptoms of certain mental health disorders. In this study, we review the status and usage of psilocybin in clinical practice preceding and following the COVID-19 pandemic. The search criteria for the study included psilocybin or psychedelics or psychedelic-therapy psychiatry and long-haul COVID. The search spanned English articles from January 2020 to April 2024, utilizing the PsychInfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PubMed databases. Two reviewers independently screened each record to decide if a study met the inclusion criteria and to account for bias. Each article researched different pathologies, including depression, anxiety, post-traumatic stress disorder, and COVID-19. The manuscripts collectively emphasize that there is evidence that psilocybin has a role in the treatment of said pathologies, with relatively safe outcomes if administered under proper medical supervision. Psilocybin use was followed up for a relatively long period after some trials, but further research is warranted to draw a more definitive conclusion regarding the therapeutic uses of psilocybin. Our review reflects that barriers to using psilocybin therapeutically for long-haul COVID-19 exist, which significantly impacts the scope of our research. While evidence suggests its efficacy in mental health conditions such as depression and mood disorders, more robust clinical trials are needed. Current literature supports the pharmacological basis that psilocybin may be effective in treating COVID-19 sequelae. Psilocybin’s role in inhibiting SARS-Cov-2 protease shows promise, but ultimately, in vitro validation will be necessary before wider approval of the drug. Lastly, large clinical trials comparing psilocybin to standard care and assessing symptom relief in long-term COVID patients may help validate the findings seen in much of the current literature.

## Linked entities

- **Chemicals:** psilocybin (PubChem CID 10624)
- **Diseases:** COVID-19 (MONDO:0100096), depression (MONDO:0002050), anxiety (MONDO:0005618), post-traumatic stress disorder (MONDO:0005146)

## Full-text entities

- **Diseases:** post-traumatic stress disorder (MESH:D013313), mood disorders (MESH:D019964), depression (MESH:D003866), Post-COVID Syndrome (MESH:D000094024), mental health disorders (OMIM:603663), COVID-19 (MESH:D000086382), anxiety (MESH:D001007)
- **Chemicals:** Psilocybin (MESH:D011562)
- **Species:** Gammacoronavirus (genus) [taxon 694013], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606], Agaricus bisporus (common mushroom, species) [taxon 5341]

## Full text

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## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12289454/full.md

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Source: https://tomesphere.com/paper/PMC12289454