The Effects of Psilocybin on Lipopolysaccharide-Induced Inflammation in THP-1 Human Macrophages
Esmaeel Ghasemi Gojani, Bo Wang, Dongping Li, Olga Kovalchuk, Igor Kovalchuk
Psychoactives January 28, 2024 DOI: 10.3390/psychoactives3010004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | THP-1 human monocyte cell line differentiated into macrophages |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Thp1 cell line Lipopolysaccharide Inflammation |
| Citations | 12 |
| Key findings | Psilocybin dose-dependently reduces LPS-induced proinflammatory cytokine and protein production in THP-1 macrophages, likely through modulation of NF-κB, IL-6/TYK2/STAT3, and TYK2/STAT1 signaling pathways. |
Abstract
Psilocybin, an innate compound produced by mushrooms belonging to the Psilocybe genus, is primarily known for its agonistic effects on the serotonin 5-HT2A receptor. This receptor’s functioning is involved in many neurological processes. In the context of this research, our primary aim was to comprehensively investigate the influence of psilocybin as a serotonin receptor agonist on the intricate cascade of events involved in THP-1 macrophages stimulated by lipopolysaccharide (LPS). THP-1 monocyte cells were subjected to differentiation into macrophages through a controlled incubation with phorbol 12-myristate 13-acetate (PMA). The next step involved the induction of an inflammatory response by exposing THP-1 macrophages to 500 ng/mL LPS for 4 h. Subsequently, we triggered the activation of the second phase of the NLRP3 inflammasome by introducing adenosine triphosphate (ATP) immediately following LPS stimulation. Our findings have revealed a dose-dependent inverse correlation between psilocybin exposure and the production of LPS-induced proinflammatory cytokines and proteins. Our work indicates that psilocybin likely mediates these responses by influencing key signaling pathways, including NF-κB, IL-6/TYK2/STAT3, and TYK2/STAT1.