The SARS-CoV-2 epidemic has increased the number of people experiencing depression, with about one third of the global population affected by mental health symptoms such as depression and anxiety. S-ketamine, approved by the FDA in March 2019 for drug-resistant depression, offers a rapid antidepressant effect, reaching maximum effectiveness within 24 hours and possibly reducing suicidal thoughts. However, further research on its side effects is needed, particularly for individuals prone to psychosis or those using alcohol or psychoactive substances.
Aging involves chronic low-grade inflammation that contributes to depression and neurodegenerative diseases like Alzheimer's and Parkinson's. Psilocybin, acting through its active metabolite psilocin as a partial agonist at the 5-HT2A receptor, may address these challenges by modulating cortical glutamate transmission, enhancing TrkB/BDNF pathways, and influencing neuroimmune cascades including NF-κB. Human studies report acute reductions in TNF-α with variable effects on IL-6 and CRP. Psilocybin's rapid onset, short half-life, and phase-II glucuronidation reduce drug interaction risks, making it potentially advantageous for older adults. Controlled studies show rapid antidepressant and anxiolytic effects in major depressive disorder, treatment-resistant depression, and existential distress, with emerging signals in neurodegeneration. The review integrates current evidence and calls for targeted studies in older adults.