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.
