Can Psilocybin Extend Lifespan? Exploring the Science Behind the Latest Longevity Study

In a landmark study published in Nature Aging (June 2025), researchers reported the first experimental evidence that microdoses of psilocybin—an active compound found in psychedelic mushrooms—extended the lifespan of both human STEM cells and mice in a dual-model design study This unexpected discovery has sparked global attention, opening the door to new research on how psychedelics may influence aging, brain health, and resilience against neuro-degeneration.

We’ll break down the study’s findings, explore its implications for future therapies, and discuss how other functional mushrooms, like Lion’s Mane, offer legal, well-tolerated options for supporting cognitive health today.

The Study at a Glance: Psilocybin and Lifespan Extension

• Source: Nature Aging, 2025 – "Microdose psilocybin extends lifespan of human brain organoids by preserving cellular integrity."
• Models Used:
  • Human Cortical Organoids – Grown from induced pluripotent stem cells (iPSCs), these 3D brain-like tissues were treated with microdoses of psilocybin.
  • Aged Mice – Male mice were given 5 mg/kg of psilocybin every third day for 4 weeks, then monthly high doses of 15mg/kg for ten months.
• Outcomes:
  • Organoids: Lived up to 22% longer than controls, with greater mitochondrial stability, lower oxidation rates, and favorable gene expression changes linked to neuroprotection & neuroplasticity.
  • Mice: Showed improved survival rates, enhanced motor coordination, and reduced signs of neuroinflammation.

Figure 2: Psilocybin treatment in aged mice extends lifespan.

This is the first peer-reviewed evidence that a psychedelic compound can impact cellular longevity in human neural tissues and in an actual organism. While early-stage, the implications for aging and neurodegenerative diseases are profound.

Psilocybin’s Effects on Mood and Mental Health

While lifespan extension is a novel application, psilocybin’s effects on the brain have been studied for decades, particularly in mental health:

• Major Depressive Disorder (MDD): A 2023 study published in JAMA found that a single 25 mg dose of psilocybin produced rapid and sustained reductions in depressive symptoms over a six-week period, outperforming placebo in a randomized controlled trial.
• Post-Traumatic Stress Disorder (PTSD): According to a 2021 report in Translational Psychiatry, psilocybin-assisted therapy significantly reduced PTSD symptoms in veterans, with improvements maintained at the six-month follow-up.
• Brain Connectivity: Imaging studies have shown psilocybin promotes neural plasticity and reorganization, especially in the default mode network (DMN)—the area often dysregulated in depression and anxiety.
• Emotional Regulation: A 2024 study completed by the University of Copenhagen Denmark found that Psilocybin helped to regulate the Amygdala (fight-or-flight) response. 26 healthy patients were given microdoses and then underwent an MRI. The psilocybin group showed significantly decreased amygdala activation (mean change -0.54, p = 0.03)

These mood-regulating and connectivity-enhancing properties may be part of why psilocybin also showed protective effects in the recent longevity study.

Psilocybin, Telomeres, and Cellular Lifespan

One of the most intriguing revelations from the 2025 Nature Aging study was that psilocybin microdosing appeared to extend the lifespan of human brain organoids by preserving telomere length—a critical marker of cellular aging.

Telomeres are protective caps on the ends of chromosomes that shorten each time a cell divides. When telomeres become too short, the cell can no longer replicate and enters senescence or dies. In the study, organoids treated with psilocybin showed greater telomere stability, suggesting the compound may reduce cellular stress or oxidative damage—two of the primary accelerants of telomere shortening.

This adds a new dimension to psilocybin’s profile, not just as a mental health agent but as a potential longevity-supportive molecule at the cellular level. While still preliminary, this line of research raises the possibility that psilocybin could contribute to slowing neurobiological aging over time.

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Repairing the Brain: Psilocybin and Neuroplasticity After Trauma

Credit: University of Copenhagen - Denmark

Beyond cell-level effects, psilocybin has demonstrated a powerful ability to reshape brain connectivity and support recovery from trauma. This is particularly relevant for individuals with conditions like PTSD, depression, or traumatic brain injury (TBI).

• Prefrontal Cortex (PFC): Often underactive in mood disorders. Psilocybin boosts connectivity between the Frontal Cortex and other regions, helping restore emotional regulation and executive function.
• Amygdala: Hyperactivity here is linked to fear and anxiety. Psilocybin has been shown to reduce amygdala response to threatening stimuli, calming emotional reactivity.
• Default Mode Network (DMN): This circuit is involved in self-referential thinking and often loops negative thought patterns in depression. Psilocybin temporarily “resets” the DMN, disrupting these loops and increasing global brain connectivity.
• Hippocampus: Crucial for memory and emotional learning. Psilocybin may enhance hippocampal neurogenesis, supporting the formation of new, more adaptive memories after trauma.

Through these effects, psilocybin appears to promote neuroplasticity—the brain’s ability to reorganize and form new neural pathways. This suggests real potential not just for symptom relief, but for deep, structural healing in the brain.

Why Lion’s Mane Is Worth Your Attention Too

If you're not in a location where psilocybin is legal—or prefer to stick to functional mushrooms with centuries of traditional use—Lion’s Mane (Hericium erinaceus) is a powerful, legal alternative.

• Neurogenesis Support: Lion’s Mane has been shown to stimulate nerve growth factor (NGF) production, a protein vital for the maintenance and regeneration of neurons.
• Cognitive Function: Human clinical trials have found that daily supplementation may improve mild cognitive impairment in older adults.
• Mood Balance: Preclinical studies suggest Lion’s Mane may support hippocampal regeneration and reduce depressive behavior in animal models.

And unlike psilocybin, Lion’s Mane is non-psychedelic, well-tolerated, and widely available in capsule or powdered form. If you want to learn more read our blog on Lion's Mane here

Looking Ahead: What This Means for Brain Health and Aging

This emerging research on psilocybin’s cellular effects adds fuel to a broader conversation: how do we protect the brain as we age? With neurodegenerative conditions like Alzheimer’s and Parkinson’s on the rise, there’s urgent need for new interventions that do more than just mask symptoms.

Whether through psychedelic research or functional mushrooms like Lion’s Mane, the goal is the same: extend cognitive healthspan, protect brain tissue, and support emotional well-being.

We’ll be tracking this field closely as new clinical studies emerge—and sharing practical, legal ways you can support your brain along the way.

Further Reading:

• Can Mushrooms Help the Brain Heal? The Science of NGF and Lion’s Mane

• Creatine for the Brain: How This Supplement Supports Cognition and Aging

• Our Lion's Mane + Niacin Capsules

Citations:

1. Kato, K., Kleinhenz, J.M., Shin, YJ. et al. (2025) Psilocybin treatment extends cellular lifespan and improves survival of aged mice. npj Aging 11, 55. https://doi.org/10.1038/s41514-025-00244-x
2. Raison CL, Sanacora G, Woolley J, et al. (2023) Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023;330(9):843–853. doi:10.1001/jama.2023.14530
3. Doss, M.K., Považan, M., Rosenberg, M.D. et al. (2021) Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder. Transl Psychiatry 11, 574. https://doi.org/10.1038/s41398-021-01706-y

4. Armand, S., Larsen, K., Madsen, M. K. et al. (2024). Amygdala response to emotional faces following acute administration of psilocybin in healthy individuals. Neuroscience Applied, 3, 103934. https://doi.org/10.1016/j.nsa.2023.103934

5. Khan, A.J., Bradley, E., O’Donovan, A., Woolley, J. (2022). Psilocybin for Trauma-Related Disorders. In: Barrett, F.S., Preller, K.H. (eds) Disruptive Psychopharmacology . Current Topics in Behavioral Neurosciences, vol 56. https://doi.org/10.1007/7854_2022_366

6. Ling, S., Ceban, F., Lui, L.M.W. et al. (2022). Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression. CNS Drugs 36, 17–30. https://doi.org/10.1007/s40263-021-00877-y

7. Simon B. Goldberg, Brian T. Pace, Christopher R. Nicholas, Charles L. Raison, Paul R. Hutson, (2020). The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis, Psychiatry Research, Volume 284, 2020,112749, https://doi.org/10.1016/j.psychres.2020.112749.

 

Disclaimer:

This blog post is intended for informational and educational purposes only. It does not constitute legal advice, medical guidance, or a recommendation for the use of any controlled substance.

Psilocybin and other psychedelic compounds referenced herein are classified as Schedule I substances under U.S. federal law and are illegal to possess or use in the state of Texas outside of approved clinical research settings.

The content shared in this article is based on publicly available, peer-reviewed scientific research and is not an endorsement of any illegal activity or unregulated use.

Happenstence does not manufacture, sell, or distribute psilocybin or any psychedelic substances.

The author’s views do not represent any governmental body or employer. If you are a public employee, healthcare provider, or government worker, you are advised to consult your agency’s ethics policy before engaging with or sharing content on this topic.

These statements have not been evaluated by the Food and Drug Administration. This content is not intended to diagnose, treat, cure, or prevent any disease.