Deciphering psilocybin: Cytotoxicity, anti-inflammatory effects, and mechanistic insights
Salma Laabi, Claire LeMmon, Callie Vogel, Mariana Chacon, Víctor M. Jiménez
International Immunopharmacology February 23, 2024 DOI: 10.1016/j.intimp.2024.111753 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | RAW 264.7 murine macrophages |
| Interventions | Psilocybin Psilocin |
| Duration | 4-hour incubation |
| Topics | Psilocybin |
| Keywords | Pharmacology Cytokine Hallucinogen Cytotoxicity |
| Citations | 16 |
| Key points | Psilocin, but not psilocybin, exerts anti-inflammatory effects on classically activated macrophages by reducing TNF-α and increasing IL-10 production. |
Abstract
A decade of clinical research has indicated psilocybin's effectiveness in treating various neuropsychiatric disorders, such as depression and substance abuse. The correlation between increased pro-inflammatory cytokines and the severity of neuropsychiatric symptoms, along with the known anti-inflammatory potential of some psychedelics, suggests an immunomodulatory role for psilocybin. This study aims to understand the mechanism of action of psilocybin by investigating the cytotoxic and immunomodulatory effects of psilocybin and psilocin on both resting and LPS-activated RAW 264.7 murine macrophages. The study evaluated the cytotoxicity of psilocybin and psilocin using an LDH assay across various doses and assessed their impact on cytokine production in RAW 264.7 cells, measuring cytokine expression via ELISA. Different doses, including those above and below the LC50, were used in both pre-treatment and post-treatment approaches. The LDH assay revealed that psilocybin is almost twice as cytotoxic as psilocin, with an LC50 of 12 ng/ml and 28 ng/ml, respectively. In resting macrophages, both psilocybin and psilocin triggered significant release of TNF- α after 4 h, with the lowest doses inducing higher levels of the cytokine than the highest doses. IL-10 expression in resting cells was only triggered by the highest dose of psilocin in the 4-hour incubation group. In LPS-stimulated cells, psilocin reduced TNF- α levels more than psilocybin in pre-treatment and post-treatment, with no significant effects on IL-10 in pre-treatment. Psilocin, but not psilocybin, induced a significant increase of IL-10 in post-treatment, leading to the conclusion that psilocin, but not psilocybin, exerts anti-inflammatory effects on classically activated macrophages.
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 15
- Psychedelics in neuroinflammation: Mechanisms and therapeutic potential Progress in Neuro-Psychopharmacology and Biological Psychiatry January 31, 2025
- 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
- The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies Progress in Neuro-Psychopharmacology and Biological Psychiatry September 7, 2024
- Psilocybin and psilocin regulate microglial immunomodulation and support neuroplasticity via serotonergic and AhR signaling. International Immunopharmacology June 26, 2025
and 10 more in the library
Cites 47
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
and 42 more in the library