Psilocybin

Fungi, especially mushrooms, are the principal source of naturally occurring psychedelics (1):

• the mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions
  
• the Psilocybe cubensis mushroom is the most widespread species of the Psilocybe genus
  
• structure of psilocybin is such that it cannot cross the blood-brain barrier
  • the metabolite of psilocybin, psilocin, is more lipophilic and therefore more active (2)
    • the active metabolite can be found 20-40 minutes after ingestion as psilocybin is quickly converted to its metabolite in the stomach acid or via first-pass metabolism with a bioavailability of around 50% and a half-life of 2.5 hours
      
• psilocybin can be produced synthetically
  
• psilocybin therapy produces rapid and persistent antidepressant effects in major depressive disorder (MDD) (3)
  • six-week intensive treatments with either psilocybin or escitalopram (with psychological support) for MDD were associated with long-term improvements in depressive symptom severity (3)

Reference:

1. Lowe H, Toyang N, Steele B, Valentine H, Grant J, Ali A, Ngwa W, Gordon L. The Therapeutic Potential of Psilocybin. Molecules. 2021 May 15;26(10):2948.
2. Ziff S, Stern B, Lewis G, Majeed M, Gorantla VR. Analysis of Psilocybin-Assisted Therapy in Medicine: A Narrative Review. Cureus. 2022 Feb 5;14(2):e21944.
3. Erritzoe E et al. Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial. Lancet; published online September 21 2024.