From fungi to pharmacy: Applied technologies in psilocybin production and its therapeutic applications
DOI:
https://doi.org/10.55674/cs.v18i1.264689Keywords:
Psilocybin, Synthetic Biology, Psychedelic-Assisted Therapy, Major Depressive DisorderAbstract
Psilocybin, a naturally occurring tryptamine alkaloid found in over 200 species of fungi, has emerged as a focal point in the modern revival of psychedelic science. Once relegated to the margins of psychopharmacology due to its association with counterculture and strict legal restrictions, psilocybin is now undergoing a scientific renaissance. This transformation is driven by its unique pharmacological profile and promising therapeutic potential across a range of psychiatric and neurodegenerative conditions. This review systematically summarizes the research progress on psilocybin, covering its natural biosynthetic pathways, production technologies, mechanisms of action, and clinical applications. We first introduced its four-enzyme synthesis pathway in Psilocybe fungi and explored how synthetic biology can revolutionize its production methods through microbial heterologous expression. Pharmacologically, psilocybin acts as a prodrug that is converted in vivo into its active metabolite, dephosphorylated psilocybin (psilocin), which functions as a partial agonist of the 5-HT2A receptor. This activates neuroplasticity pathways such as BDNF and mTOR, thereby producing rapid and sustained antidepressant effects. Despite its therapeutic promise, significant challenges remain. These include methodological limitations such as functional unblinding in clinical trials, lack of diversity in study populations, and evolving regulatory frameworks. Looking forward, the integration of precision psychiatry, synthetic biology, and novel trial designs will be critical in translating psilocybin from a promising compound into a mainstream therapeutic agent. This review aims to provide a foundational understanding of psilocybin’s scientific basis and its potential to reshape modern psychiatric care, we uniquely bridge the gap between upstream biosynthetic engineering and downstream clinical efficacy, providing a holistic roadmap for the drug’s development from fungi to pharmacy.
GRAPHICAL ABSTRACT
HIGHLIGHTS
- Microbial biosynthesis enables scalable, high-titer psilocybin production.
- Therapeutic action is driven by 5-HT2A receptor-mediated neuroplasticity.
- Demonstrates rapid and sustained antidepressant efficacy in clinical trials.
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