Network pharmacology and molecular simulation reveal the entourage effect mechanisms of psilocybin-producing mushrooms on the brain
Scientific Reports February 14, 2026 Zurika Murray, Angélique Lewies, Johannes F. Wentzel et al. 3 citations
Whole mushroom extracts containing psilocybin may be more effective than isolated psilocybin for treating psychiatric disorders, possibly due to an entourage effect from additional bioactive compounds. Using computational methods including network pharmacology, molecular docking, and molecular dynamics, researchers identified fifteen compounds from psilocybin-producing mushrooms, eight with favorable pharmacokinetic profiles. Target prediction revealed 44 brain-localized proteins with biological connectivity. The compounds showed strong docking to neurological targets, with several forming stable salt bridges with the Asp155 residue of HTR2A, similar to serotonin. Molecular dynamics simulations confirmed high residence stability within HTR2A and MAOA binding pockets, supporting a mechanistic rationale for enhanced efficacy of whole mushroom extracts.