In a small pilot sample of two older adults with amnestic mild cognitive impairment and three healthy controls, two doses of 25 mg psilocybin given one week apart were safe and well tolerated, with no unexpected or serious adverse events. Expected side effects included dizziness and altered perception, all of which resolved without lasting effects. This double-blind, placebo-controlled randomized study uses PET imaging to measure psilocybin's effect on synaptic density in the hippocampus and prefrontal cortex, and whether changes relate to improved cognition. Preliminary findings support the feasibility of investigating psilocybin in supervised medical settings as a potential treatment for amnestic mild cognitive impairment.
A systematic review of 42 clinical studies involving 1,068 participants found that psilocybin, when administered in controlled settings, has a favorable safety profile. Common adverse events included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. Serious adverse events were reported infrequently, in only 2 of the 42 studies, and were limited to participants with underlying depressive disorders, such as suicidal behavior or hospitalization. All studies had a high risk of bias due to concerns regarding blinding. The review provides an outline of common and uncommon adverse events, serious adverse events, and considerations for future protocols.