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Danielle Bukovsky1,2, Aron Amaev1,2, Jianmeng Song1

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Summary
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Psilocybin shows promise as a safe and well-tolerated treatment for amnestic mild cognitive impairment (aMCI). Further research is warranted to explore its potential in improving cognitive function and counteracting neurodegeneration in aMCI patients.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Clinical Trials

Background:

  • Amnestic mild cognitive impairment (aMCI) is a precursor to Alzheimer's Disease, characterized by synaptic loss and cognitive decline.
  • Current treatments for aMCI lack efficacy, highlighting the need for novel therapeutic approaches.
  • Psilocybin, a psychedelic compound, is being investigated for neuropsychiatric disorders, potentially acting via the 5HT2A serotonin receptor (5HTA-R).

Purpose of the Study:

  • To assess psilocybin's effect on synaptic density in the hippocampus and prefrontal cortex of aMCI patients using PET imaging.
  • To determine if changes in synaptic density are associated with improved cognitive outcomes in aMCI.
  • To evaluate the safety and tolerability of psilocybin in individuals with aMCI.

Main Methods:

  • A double-blind, placebo-controlled randomized PET study utilizing the radioligand [18F]SynVesT.
  • Participants with aMCI and healthy controls received two doses of 25mg psilocybin or placebo.
  • PET scans were conducted pre- and one-week post-treatment, with clinical and neuropsychological assessments at multiple time points.

Main Results:

  • Pilot data from aMCI participants and healthy controls indicate psilocybin was well-tolerated.
  • No unexpected or serious adverse events (AEs) were reported; expected AEs like dizziness and altered perception resolved without sequelae.
  • All participants completed study procedures, and blinding remained effective.

Conclusions:

  • Preliminary findings suggest psilocybin is safe and well-tolerated in older adults with aMCI.
  • The study demonstrates the feasibility of investigating psilocybin in a supervised medical setting for aMCI.
  • Psilocybin presents a potential novel treatment strategy for aMCI, warranting further investigation.