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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 10
- Psychedelics in neuroinflammation: Mechanisms and therapeutic potential Progress in Neuro-Psychopharmacology and Biological Psychiatry January 31, 2025
- Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HT2 Receptor-Dependent Manner Molecules October 28, 2024
- The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies Progress in Neuro-Psychopharmacology and Biological Psychiatry September 7, 2024
- Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics. Progress in Neuro-Psychopharmacology and Biological Psychiatry August 30, 2024
- Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HT2A receptor psychedelics from a transdiagnostic perspective. Acta Neuropsychiatrica July 25, 2025
and 5 more in the library
Cites 7
- The pharmacology of psilocybin Addiction Biology October 1, 2002
- The Therapeutic Potential of Psilocybin Molecules May 15, 2021
- Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression CNS Drugs November 17, 2021
- Psilocybin, psychological distress, and suicidality Journal of Psychopharmacology September 1, 2015
- Phytochemical, Cytotoxicity, Antioxidant and Anti-Inflammatory Effects of Psilocybe Natalensis Magic Mushroom Plants August 31, 2020
and 2 more in the library