Psilocybin decelerates cellular senescence
Louise Hecker, Kosuke Kato, Jennifer Kleinhenz, Yoon-Joo Shin, John Papageorgiou, Ali J Zarrabi
Research Square June 27, 2023 preprint DOI: 10.21203/rs.3.rs-2921423/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study |
|---|---|
| Population | Human cells in a model of replicative senescence |
| Intervention | Psilocybin |
| Duration | Continuous treatment throughout replicative cellular lifecycle |
| Topics | Psilocybin |
| Keywords | Senescence Hallucinogen Pharmacology |
| Key findings | Psilocybin treatment decelerates cellular senescence in a human cell model, reducing senescence markers and oxidative stress without senolytic activity. |
Abstract
Abstract Psilocybin is the psychoactive substance contained in the psilocybe(hallucinogenic) mushroom, which has received considerable attention among the scientific community in recent years. Human studies have demonstrated that even a single-dose of psilocybin can improve debilitating physical and psychological symptoms with durable long-term effects. >136 clinical studies with psilocybin have been completed or are ongoing for various indications, including psychiatric, neurodegenerative, chronic pain, and more. However, despite considerable clinical evidence for the therapeutic effects, the underlying molecular mechanisms responsible for its beneficial actions remain enigmatic. Studies with psilocybin have overwhelmingly focused on neurological impacts and/or behavioral outcomes; however, few studies have evaluated other mechanisms by which it exerts beneficial effects. It has recently been hypothesized that psilocybin may exert beneficial effects on aging; however, no studies have experimentally investigated the impact of psilocybin on senescence/aging. Using a previously validated human cell model of replicative senescence in vitro, cells were treated with psilocybin continuously throughout their replicative cellular lifecycle. Psilocybin treatment led to a dose-dependent decrease in cell-cycle arrest markers, increased markers of DNA replication and proliferation, reduced senescence-associated secretory phenotype (SASP), and reduced oxidative stress levels. Further, psilocybin did not demonstrate senolytic activity. Overall, these data are the first experimental evidence suggesting that psilocybin may decelerate the process of cellular senescence. Given that senescence and inflammation contribute to the pathogenesis of numerous age-related diseases, these studies could lay the foundation for the use of psilocybin as a therapeutic strategy for many age-related disease indications and/or as a geroprotective agent.
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
Cites 11
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study Psychopharmacology March 1, 2004
- The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act Neuropharmacology June 5, 2018
- Classical psychedelics for the treatment of depression and anxiety: A systematic review. Journal of Affective Disorders November 1, 2019
- Long-term effects of psychedelic drugs: A systematic review Neuroscience & Biobehavioral Reviews March 16, 2020
and 6 more in the library