League Ivy and Lion's Mane(Hericium erinaceus) Лига плюща и гривы.

Pharmacological Analogues of Erinacine A and Hericenones from Hericium erinaceus: Rational Design of Non-Psychedelic Neurotrophic, Nootropic, Antidepressant, Synaptogenic, Myelinogenic, Geroprotective and Telomerase-Activating Agents
Yaroslav Grigorievich Zaitsev ORCID: 0000-0002-0069-2997
Preprint · December 2025

Abstract
Erinacine A and psilocybin exhibit partially overlapping pharmacological profiles, but differ significantly in lipophilicity and the type of neuroplasticity induced. The fundamentally similar carvacrol and asarone also demonstrate potential as neurotrophic agents, forming a number of pharmacophore assemblies and pharmacological strategies that have formed the basis of rational drug design.
Fast neuroplasticity (psilocybin, ketamine) promotes synaptogenesis but can duplicate pathological connections and increase neural noise. In contrast, slow neuroplasticity—true neurogenesis and myelinogenesis—appears to be beneficial in organic brain damage, depression, Alzheimer's disease, and related conditions. The lipophilic and amphiphilic synthetic terpenes and tryptophols presented in this study are targeted at deep neurotrophic activity, primarily targeting 5-HT1A serotonin receptors, both through penetration into deep brain regions and through their high affinity for 5-HT1A receptors in silico analysis (https://serotoninai.streamlit.app/).
The structures exhibit particularly low, low, and high affinity, high lipophilicity, and bioavailability. They also possess significant pharmacological potential; deep penetration ensures sustained "slow neuroplasticity" with more complete 5-HT1A potential. The study also presents potential pharmacological analogs of hericenones, highly lipophilic and mobile serotonin mimetics with potential activity in myelin sheaths and within axons.

Psilocybin has also been shown to extend replicative lifespan by up to 50% through telomerase modulation and reduction of oxidative stress (presumably primarily through 5-HT1A innervation). The combined neurotrophic, nootropic, synaptogenic, myelinogenic, neuroprotective, and lifespan-extending effects of erinacine A, hericenones, and their pharmacologically related analogs make ideal candidates for next-generation therapeutics.

Keywords: erinacine A, hericenones, Hericium erinaceus, neurotrophic agents, rational drug design, non-psychedelic neuroplasticity, slow neuroplasticity, lipophilic 5-HT1A mimetics, NGF/BDNF inducers, telomerase modulation, geroprotectors