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Safety, feasibility, and tolerability of psilocybin in older adults with amnestic MCI: Preliminary data from a SV2a PET imaging study

Summary

Researchers investigated whether psilocybin, a compound from certain mushrooms, could be safely used to treat memory problems in older adults with mild cognitive impairment. In this early-stage study, participants received either psilocybin or a placebo while researchers used brain imaging to measure changes in synaptic connections. The preliminary results suggest psilocybin was well-tolerated with manageable side effects like dizziness, and participants were able to complete the study without serious problems.

Background

Amnestic mild cognitive impairment (aMCI) is characterized by synaptic loss and cognitive decline as a precursor to Alzheimer’s Disease. Current treatments such as cholinesterase inhibitors do not effectively improve cognitive or functional outcomes. Psilocybin may promote synaptogenesis through interaction with 5HT2A serotonin receptors, potentially countering neurodegenerative progression.

Objective

To assess psilocybin’s effect on synaptic density in the hippocampus and prefrontal cortex of patients with aMCI using PET imaging with [18F]SynVesT radioligand, and to determine whether these changes are associated with improved cognitive outcomes.

Results

Pilot data from two aMCI participants (mean age 71.0 years, mean MOCA 22) and three healthy controls (mean age 66.3 years, mean MOCA 27.7) showed all participants completed study procedures without issue. Psilocybin was well tolerated with no serious adverse events; expected adverse events included dizziness (n=4) and altered perception (n=3), all resolving without sequelae.

Conclusion

Preliminary data suggest psilocybin is safe, well-tolerated, and can be feasibly investigated in a supervised medical setting in older adults as a prospective treatment for amnestic mild cognitive impairment.
  • Published in:Alzheimer's & Dementia,
  • Study Type:Clinical Trial,
  • Source: 10.1002/alz70859_101101, PMC12740486
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