Temporary improvement in thinking and daily skills in advanced Alzheimer's after high-dose psilocybin mushroom use: a case report

Advanced Alzheimer’s disease imposes profound loss of autonomy, communication, continence, mobility, and social interaction, generating severe emotional and caregiving burden. Current therapeutic strategies at this stage are largely supportive, and meaningful functional recovery is generally considered unlikely. The global burden of Alzheimer’s disease and related dementias remains substantial, with major consequences for patients, families, caregivers, and health systems (Alzheimer's Association, 2024). This clinical reality has motivated growing interest in neuromodulatory and neuroplasticity-oriented approaches capable of transiently restoring residual network function.

Psilocybin produces marked alterations in large-scale brain dynamics through serotonin 5-HT2A receptor activation. Human neuroimaging studies have shown altered default mode network integrity, reduced network segregation, and broad changes in functional connectivity after psilocybin administration (Carhart-Harris et al., 2012; Madsen et al., 2021; Siegel et al., 2024; Ly et al., 2018). Preclinical studies further suggest that serotonergic psychedelics can promote structural and functional plasticity, including dendritic growth and synaptic remodeling (Vann Jones and O'Kelly, 2020).

Clinical investigation of psilocybin has focused primarily on psychiatric disorders and, more recently, on depression and anxiety in individuals with mild cognitive impairment or early Alzheimer’s disease. Published clinical data in advanced dementia remain extremely limited (Zheng et al., 2024). This report describes a case of transient multidomain functional improvement in advanced Alzheimer’s disease following high-dose psilocybin-containing mushroom administration.

The patient was an octogenarian Japanese-American woman who lived with continuous family supervision and caregiver support. Progressive cognitive and functional decline had evolved over approximately 10 years. During the preceding 5 years, verbal output became predominantly monosyllabic, accompanied by severe reduction in spontaneous interaction, chronic urinary incontinence, executive dysfunction, impaired mobility, dysphagia, and marked dependence in activities of daily living.

Observed gains were objective across autonomic, motor, executive, memory, affective, and social domains. The persistence of urinary continence after more than 5 years of chronic incontinence is particularly notable, given that continence depends on integrated interoceptive awareness, executive inhibition, and fronto-insular network function.

Recent human studies investigating psilocybin and sleep architecture have shown heterogeneous findings. In healthy volunteers, oral psilocybin increased REM sleep latency without major alterations in overall sleep–wake states (Dudysova et al., 2020). In contrast, clinical reports in depression have described improvements in sleep disturbances following psilocybin administration (Reid et al., 2024). The prolonged deep sleep-like state observed in the present patient may therefore reflect interactions between psilocybin-induced network modulation and altered baseline neurophysiology characteristic of advanced Alzheimer’s disease.

Beyond structural neuroplasticity, recent studies demonstrate marked reorganization of large-scale brain networks following psilocybin administration, including increased global integration, cortical desynchronization, and transient desegregation of canonical cortical systems (Madsen et al., 2021; Siegel et al., 2024; Ly et al., 2018; Silverstein et al., 2025). Such findings support the hypothesis that psilocybin may transiently facilitate functional reintegration of residual neural systems in neurodegenerative disease.

The present report has important limitations, including the single-case design, absence of formal polysomnographic monitoring, quantitative electrophysiology, neuroimaging biomarkers, and standardized cognitive scales. Causality cannot be established, and spontaneous fluctuations inherent to neurodegenerative disease cannot be completely excluded.

Importantly, mechanistic interpretations remain speculative. The present report should be understood primarily as a detailed observational description intended to generate hypotheses for future controlled investigation. The findings should not be interpreted as reversal of Alzheimer’s pathology. Rather, they raise the possibility that latent functional capacities may persist in advanced neurodegeneration and become temporarily accessible under specific neuromodulatory conditions.

Residual functional capacity may persist in advanced Alzheimer’s disease and may become transiently accessible following psilocybin-induced modulation of large-scale brain networks. Systematic investigation is warranted.

The author(s) declared that financial support was not received for this work and/or its publication.

The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author.

Ethical approval was not required for this single case report conducted in routine private clinical practice, in accordance with local legislation and institutional requirements. No experimental protocol or prospective research procedures were conducted. Written informed consent was obtained from the patient’s legal guardian for the publication of this case report.

ML: Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing. MC: Supervision, Validation, Writing – review & editing. JS: Supervision, Validation, Writing – review & editing.

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The author(s) declared that Generative AI was not used in the creation of this manuscript.

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