Case Report on Psilocybin and Alzheimer’s Disease

A recent case report published in Frontiers in Neuroscience discusses how a high dose of psilocybin mushrooms seemingly provided temporary improvements in daily functions and communication skills for a patient with advanced Alzheimer’s disease. This raises intriguing possibilities that some brain networks may still retain dormant functions, even in severe neurodegeneration.

This finding not only suggests new methods for symptom management but also lays groundwork for future clinical trials. There’s an increasing scientific interest in the therapeutic uses of psychedelic compounds.

Alzheimer’s disease, a progressive condition, gradually deteriorates memory, thinking, and daily functioning. In its advanced stages, individuals often lose significant autonomy, face limited communication, and heavily rely on caregivers. Current treatments mainly focus on supportive care since substantial recovery from lost functions is seen as unlikely.

This disease involves a decline in neuroplasticity—the brain’s ability to forge new connections and adapt. Patients lose synapses, where neuron communication occurs, while specific proteins accumulate and brain inflammation increases.

Many Alzheimer’s patients also suffer from depression and anxiety, which can accelerate cognitive decline. To find alternative management methods, a team of researchers investigated psilocybin, a naturally occurring psychedelic found in certain “magic” mushrooms.

Marcos Lago, a psychiatrist and clinical researcher in São Paulo, Brazil, led this observational study. He mentioned that this case arose during routine patient care.

“My clinical work with psilocybin, coupled with my interest in consciousness and neuroplasticity, led me to wonder if some abilities might still exist but remain inaccessible in advanced Alzheimer’s,” Lago explained. “We felt it was important to document this scientifically due to the unexpected changes observed after the session.”

The researchers referenced a 2024 review that noted psilocybin metabolizes into psilocin, an active compound that crosses the blood-brain barrier and interacts with the 5-HT2A serotonin receptor. This activation might stimulate neuroplasticity and temporarily change extensive brain networks, including the default mode network, linked to mind-wandering and self-reflection.

Preliminary studies indicate that psilocin could encourage the growth of new dendritic spines on neurons, aiding signal transmission. This process involves releasing glutamate and activating proteins like brain-derived neurotrophic factor, supporting neuron survival and synapse remodeling.

Moreover, psilocybin might also reduce neuroinflammation by regulating microglial cell activity. In Alzheimer’s, these cells often become overactive in response to protein deposits and worsen brain tissue damage. Psilocybin has been shown to lower the production of pro-inflammatory cytokines, potentially alleviating harmful immune responses.

This potential to induce structural brain changes prompted the authors to observe the effects of a high dose of psilocybin on a patient with severe dementia. Current research on psilocybin primarily focuses on psychiatric disorders like severe depression, with limited data on its use for advanced dementia cases.

The research team studied an 80-year-old Japanese-American woman who had shown steady cognitive and functional decline over ten years, eventually diagnosed with advanced Alzheimer’s disease. For five years prior to the study, she had faced significant physical and cognitive challenges, requiring constant care.

Her baseline included chronic urinary incontinence, difficulty swallowing, no ability to walk independently, and a notably flat emotional state. Communication had significantly diminished, limited mainly to monosyllabic responses, and she required full support for daily living tasks.

The researchers provided a single oral dose of five grams of psilocybin mushrooms, using a specific cultivated strain called Enigma. The observational nature of the study was due to the absence of an established dosing guideline for psilocybin in advanced dementia cases.

During the acute phase, the patient exhibited several strong physical responses, including sweating and a prolonged state resembling deep sleep. Around 19 hours post-administration, she unexpectedly woke and engaged in an autobiographical conversation that lasted for several hours.

In the days and weeks that followed, the researchers noted several functional improvements in both cognitive and physical areas. The patient regained urinary control, a function lost for five years, and began walking independently. Her emotional responsiveness improved too, as she made eye contact and smiled more.

“What surprised us the most was the range of changes,” Lago remarked to PsyPost. “The patient engaged in spontaneous conversation, improved social interaction and mobility, and regained urinary continence after years of impairment.”

“Any one of these changes could have been seen as a fluctuation, but their convergence across multiple domains stood out,” Lago noted, adding that these observations were primarily clinical and not measured through standardized tests.

Additionally, improvements in working memory and episodic memory were documented. The patient recognized vehicles and asked contextual questions about individuals. Notably, since some improvements, especially urinary continence, persisted for a month, the team conducted a second supervised session with a lower dose of three grams.

During this second session, the patient was much more verbally expressive. She shared positive images, like surfing with her son on a tranquil island, exhibited humor, and demonstrated greater walking agility, even stating that the experience was enjoyable.

“This case is remarkable because the patient had advanced Alzheimer’s with significant impairments but then showed transient gains. That’s extraordinary. Yet, as a neuroscientist studying serotonin signaling, I’m not shocked that a potent serotonergic psychedelic could reorganize brain activity and occasionally reveal seemingly lost capacities,” remarked Dustin Hines, an associate professor at the University of Nevada, Las Vegas, who wasn’t involved in the study.

While the report records unusual functional gains, the authors acknowledge multiple limitations in its design. Since it examines only one individual, the findings aren’t broadly applicable to all Alzheimer’s patients. There was also a lack of thorough clinical monitoring tools, such as brain imaging or standardized cognitive assessments.

“There are significant limitations,” Lago admitted. “This was a single case, lacking a control group or placebo, meaning causality can’t be determined and the findings can’t easily be generalized. We primarily relied on clinical observations and caregiver reports, without neuroimaging or biomarkers.”

Spontaneous fluctuations in cognitive and physical states in neurodegenerative diseases are possible, so these natural variations might also account for the patient’s temporary improvement. Plus, using mushroom preparations leads to variability in dose standardization compared to pharmaceutical-grade psilocybin.

The researchers caution against misinterpreting these results as a cure for Alzheimer’s pathology. The underlying brain damage, such as amyloid and tau protein accumulation, wasn’t measured and remains unresolved. Instead, the case suggests that some latent functional abilities might still exist in the brain during late-stage neurodegeneration.

“The key takeaway isn’t that psilocybin has been proven to treat Alzheimer’s disease,” Lago clarified. “This case hints that some abilities might still be accessible, even in advanced stages, implying that severe dementia doesn’t always mean complete loss of previously acquired functions.”

“However, this case is merely a hypothesis generator and shouldn’t be viewed as evidence of an established treatment,” he emphasized. “This was not conducted as a clinical trial, so interpreting it as proof of psilocybin’s effectiveness for Alzheimer’s is misleading.”

Case reports can be quite beneficial in the medical field for generating hypotheses and directing scientific exploration into new areas. The temporary improvements seen in this patient suggest that certain dormant capabilities in the brain may become accessible under specific conditions that alter network dynamics. The authors stress that controlled clinical trials are now essential to better assess the safety, efficacy, and mechanisms of psilocybin in advanced dementia cases.

“The next vital step would be formal research done under ethical oversight,” Lago proposed. “Initial studies should prioritize safety and feasibility, selecting participants carefully, standardizing preparations, and employing objective cognitive measures with longer follow-ups, including neuroimaging and biomarkers whenever feasible.”

The scientists are eager to uncover the physiological factors influencing this phenomenon. “The broader question is whether functional networks can be re-engaged in advanced neurodegenerative disease, and if so, under what conditions,” Lago added.

That said, the authors wish to remind readers that this report remains strictly observational and carries accompanying risks. “Families and patients shouldn’t interpret this document as an endorsement for unsupervised use,” Lago stated. “Older adults with advanced neurodegenerative diseases can be medically vulnerable, and the safety of psilocybin for this group largely remains unverified.”

“This case underscores a phenomenon worthy of deeper exploration,” he concluded. “It doesn’t offer a clinical protocol or validate a treatment.”

In a related effort to examine how psychedelics can affect aging brains, researchers at the UC Berkeley Center for the Science of Psychedelics have initiated the PLASTICITY study, the first psychedelic neuroimaging trial aimed specifically at healthy older adults. Given that older populations have often been excluded from psychedelics research, this study will explore whether synthetic psilocybin can enhance neuroplasticity and counteract structural brain changes associated with aging.

Participants aged 60 to 85 will receive doses ranging from 1 to 30 milligrams of psilocybin, with advanced MRI and cognitive assessments before and after the intervention to track shifts in memory, perception, and emotional regulation. The interdisciplinary team hopes to determine whether positive changes noted in animal studies can translate to human participants, potentially offering new strategies for promoting successful aging, improving mental well-being, and mitigating cognitive decline.

The case report titled “Transient multidomain functional improvement in advanced Alzheimer’s disease following high-dose psilocybin-containing mushroom administration: a case report” was authored by Marcos Lago, Mariana Cerveira, and Joe Xavier Simonet.