With growing evidence for psilocybin's effectiveness in treating psychiatric conditions such as major depression and substance use disorders, potential benefits of psilocybin are beginning to be examined in a wider range of medical conditions in need of novel treatments. Though psilocybin's therapeutic mechanisms are still under investigation, neuroplasticity-enhancing and anti-inflammatory effects suggest possible utility across various illnesses. This discussion will focus on two such pilot studies exploring the effects of psilocybin on mood and quality of life in people with early-stage Alzheimer's Disease and in people with chronic Lyme Disease. Preliminary results, participant reports, and clinical observations will be presented to inform the current landscape of psilocybin-assisted treatments for novel indications. https://clinicaltrials.gov/ct2/show/NCT04123314 https://clinicaltrials.gov/ct2/show/NCT05305105