The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice
Timur Zanikov, Marta Gerasymchuk, Gregory Ian Robinson, Shima Asghari, Alyssa Groves, Lucie Haselhorst, Sanjana Nandakumar, Cora Stahl, Mackenzie Cameron, Dongping Li, Alexandra Snelling, Darryl Hudson, Anna Fiselier, Olga Kovalchuk, Igor Kovalchuk, Esmaeel Ghasemi Gojani, Rocio Rodriguez‐juarez
Molecules March 14, 2023 DOI: 10.3390/molecules28062624 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | C57BL/6J mice |
| Interventions | Psilocybin Eugenol |
| Dose | 0.88 mg/kg psilocybin, 17.6 mg/kg eugenol, combinations at 1:10, 1:20, or 1:50 ratios |
| Topics | Psilocybin |
| Keywords | Eugenol Inflammation Pharmacology Lipopolysaccharide Intraperitoneal injection Western blot |
| Citations | 48 |
| Key findings | Psilocybin combined with eugenol, especially in a 1:50 ratio, reduced brain cytokine expression in mice with LPS-induced systemic inflammation. |
Abstract
Inflammation is an organism’s biological defense mechanism. Acute and chronic inflammation of the body triggers the production of pro- and anti-inflammatory pathways that can affect the content of cytokines in the brain and thus cause brain inflammation. Disorders such as depression and posttraumatic stress disorder (PTSD) are often associated with elevated inflammation. Recently, positive and promising clinical results of psilocybin for the treatment of depression and PTSD were reported. Thus, we decided to test whether psilocybin alone or in combination with eugenol, an anti-inflammatory and antioxidant agent, would prevent the increase in or decrease the content of cytokines in the brain of C57BL/6J mice injected with lipopolysaccharides (LPS). Two experiments were performed, one with pre-treatment of mice through gavage with psilocybin (0.88 mg/kg), eugenol (17.6 mg/kg), or combinations of psilocybin and eugenol (1:10, 1:20, or 1:50), followed by intraperitoneal injection of LPS, and the second, post-treatment, with initial injection with LPS, followed by treatment with psilocybin, eugenol, or their combination. Brain tissues were collected, and cytokines were analyzed by qRT-PCR, Western blot, and ELISA. Data were analyzed with a one-way ANOVA followed by Tukey’s post hoc test or with multiple unpaired t-tests. LPS upregulated mRNA expression of COX-2, TNF-α, IL-1β, and IL-6. All pre-treatments decreased the expression of COX-2 and TNF-α, with psilocybin alone and in 1:50 combination, with eugenol being the most effective. In the post-treatment, all combinations of psilocybin and eugenol were effective in reducing inflammation, with the 1:50 ratio displaying the most prominent results in reducing the mRNA content of tested cytokines. Western blot analysis confirmed the effect on COX-2 and IL-1β proteins. Finally, the ELISA showed that post-treatment with psilocybin + eugenol (1:50) demonstrated the best results, decreasing the expression of multiple markers including IL-6 and IL-8. This demonstrates the anti-inflammatory effects of a combination of psilocybin and eugenol in the brain of animals with systemically induced inflammation.
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 36
- Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain. Molecular Psychiatry July 1, 2024
- Psilocybin for the treatment of Alzheimer’s disease Frontiers in Neuroscience July 10, 2024
- Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HT2 Receptor-Dependent Manner Molecules October 28, 2024
- Anti-Inflammatory Effects of Serotonin Receptor and Transient Receptor Potential Channel Ligands in Human Small Intestinal Epithelial Cells Current Issues in Molecular Biology August 15, 2023
- The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies Progress in Neuro-Psychopharmacology and Biological Psychiatry September 7, 2024
and 31 more in the library
Cites 5
- Psychedelics as anti-inflammatory agents International Review of Psychiatry July 4, 2018
- Anti-Inflammatory Effects of Four Psilocybin-Containing Magic Mushroom Water Extracts in vitro on 15-Lipoxygenase Activity and on Lipopolysaccharide-Induced Cyclooxygenase-2 and Inflammatory Cytokines in Human U937 Macrophage Cells Journal of Inflammation Research August 1, 2021
- Phytochemical, Cytotoxicity, Antioxidant and Anti-Inflammatory Effects of Psilocybe Natalensis Magic Mushroom Plants August 31, 2020
- Psychedelics as a Treatment for Alzheimer’s Disease Dementia Frontiers in Synaptic Neuroscience August 21, 2020
- The DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype bioRxiv Preprint Server March 7, 2021