Psilocybin to promote synaptogenesis in the brains of patients with mild cognitive impairment

Abstract

Amnestic mild cognitive impairment (aMCI) may represent a prodromal stage of Alzheimer's disease dementia (ADD) for which there are no known treatments. There is renewed interest in using psychedelics, including psilocybin, to treat neuropsychiatric disorders. Evidence suggests that psilocybin exerts its psychedelic, and possibly its clinical effects, through 5HT2A serotonin receptor (5HT2A-R) agonism. Intriguingly, reduced 5HT2A-R density in the neocortex is associated with cognitive impairment. Promisingly, the results of preclinical studies suggest psilocybin may promote synaptogenesis in brain regions associated with learning and memory, possibly facilitated by 5HT2A-R agonism. As such, psilocybin is worth exploring as a novel therapeutic for aMCI to counter neurogenerative disease progression. Using a double-blind-placebo controlled design, the proposed positron emission tomography study will assess whether psilocybin increases synaptic density, as measured by the radioligand [18F]SynVesT-1, in the hippocampus and prefrontal cortex of patients with aMCI, and if changes in synaptic vesicular density are associated with improvements in cognition.