Yesterday I reported on an 80-year-old woman with advanced Alzheimer's. She hadn't spoken in full sentences for five years, was incontinent, and dependent on caregivers. But Nineteen hours after receiving 5 grams of psilocybin mushrooms, she woke up and talked for four hours. Over the following weeks she regained continence, dressed herself, made eye contact, remembered people, and laughed.
Then the effects faded.
A lot of people found this shocking. I didn't, because I've been thinking and writing about Alzheimer's as a metabolic disease for a while now. And once you understand it that way, psilocybin's potential starts to make sense.
I'm not saying it's a cure. But it appears that psilocybin may affect biological root of the disease itself.
Let me explain.
Alzheimer's Is a Metabolic Disease
The standard story of Alzheimer's is amyloid plaques accumulate, tau tangles form, neurons die, and the person slowly disappears. For decades, drug development has been based on the theory, yet it has consistently failed. And it's because they were targeting mediators, not root causes.
The more useful lens is metabolic. Alzheimer's is strongly associated with insulin resistance, mitochondrial dysfunction, neuroinflammation, and oxidative stress. This is the same cluster of dysfunctions that drives type 2 diabetes and other diseases of modern life, including psychiatric ocnditions like depression. Brain glucose metabolism shows measurable decline on PET scans years, sometimes decades, before symptoms emerge. This signifies that the brain is running out of fuel long before the person loses their memory.
This is also why severe dementia was essentially absent from ancient Greek and Roman medical records and was first described in 1906. It isn't a natural feature of ageing. It's a disease of modern environments and modern metabolic dysfunction.
What that means in practice is that neurons under chronic energy deficit don't necessarily die immediately. They downregulate their activity to survive on reduced resources. In effect, they hibernate.
This reframes what late-stage Alzheimer's is entirely. The functions that appear lost may not reflect destroyed substrate. The circuits that are still there, still structurally intact, but metabolically too compromised to fire.
As the case report showed, the woman's functions returned. That wouldn't be possible if the substrate was gone.
Psilocybin Is a Metabolic Therapy
Most people think of psilocybin as a tool that only acts on the brain. It loosens rigid thought patterns, opens a window of neuroplasticity, and allows new connections to form. All of that is correct. But two recent studies suggest the mechanism goes considerably deeper than network reorganisation in the brain.
The myelin layer. A 2026 study in Biological Psychiatry found that both psilocybin and MDMA triggered active remyelination in the hippocampus of rats. Myelin is the insulating sheath around nerve fibres that synchronises signals across brain circuits and it's what determines the timing of communication between neurons.
Myelin loss is a documented feature of Alzheimer's, and oligodendrocytes (the cells that produce myelin) are among the most metabolically demanding in the brain - meaning they are among the first to fail under energy stress. When the researchers stripped myelin experimentally, the therapeutic effects of psilocybin largely disappeared. This suggests that myelin repair is central to how the compound works.
The cellular ageing layer. A 2025 study in npj Aging found that psilocin (the active metabolite of psilocybin) extends cellular lifespan by 29-57% in human fibroblasts, and that monthly psilocybin treatment in aged mice produced 80% survival versus 50% in untreated controls.
The mechanisms involved are directly relevant to Alzheimer's: elevated SIRT1 (a master regulator of mitochondrial biogenesis), reduced Nox4 (the primary driver of cellular oxidant production), increased Nrf2 (the master antioxidant regulator), and preserved telomere length. The same 5-HT2A receptor that produces the psychedelic experience activates the SIRT1-PGC-1α axis in cortical neurons, directly improving mitochondrial function in brain cells.
In other words, psilocybin is acting on the cellular energy machinery, the oxidative stress pathways, and the myelin infrastructure that the metabolic theory identifies as the root drivers of Alzheimer's.
Why the Improvement Was Transient?
The woman's recovery didn't last indefinitely. The metabolic theory explains this cleanly.
Psilocybin can initiate remyelination, boost mitochondrial signalling, and reduce oxidative stress. But it cannot repair the underlying metabolic environment built up over a decade of insulin resistance, chronic neuroinflammation, and cellular senescence. The neurons come online. But, without a change in the underlying conditions, the system gradually retreats to its compromised baseline.
This is why I've long argued that metabolic interventions (like the ketogenic diet, intermittent fasting, cutting sugar, optimising sleep, exercise, meditation/breathwork, targeted supplementation) are foundational for healthy cognitive aging. The Bredesen protocol - which targets insulin resistance, neuroinflammation, and nutrient deficiencies simultaneously - showed nine out of ten Alzheimer's patients improving cognitively over six months. That's not a coincidence. That's metabolic restoration working.
Ultimately, I believe that psilocybin and metabolic therapy are complementary, and the regenerative window that psilocybin opens may be considerably more powerful in a brain whose metabolic soil has been rehabilitated.
The Dormant Mycelium
Mycelium under drought doesn't die. It retreats, downregulates, and waits for conditions that allow it to grow again. When moisture returns and the conditions are right, the network reactivates.
And it appears that the Alzheimer's brain does something similar.
This changes the question changes from: how can we cure Alzheimer's?
To: how can we can cultivate the conditions that allow a brain to thrive?
Sources: Lago, Cerveira & Simonet (2026), Frontiers in Neuroscience 20:1813281 | Bostancıklıoğlu et al. (2026), Biological Psychiatry DOI: 10.1016/j.biopsych.2026.01.016 | Kato et al. (2025), npj Aging 11:55