Psilocybin is gaining popularity as research shows potential benefits to those with anxiety, depression, and other mental health conditions. Individuals with risk factors for psychosis are typically excluded from such studies, limiting the empiric research of the risks and benefits in vulnerable populations. In the real-world setting, many individuals who seek treatment with psilocybin will have comorbid psychiatric conditions and other factors that predispose them to psychosis. We report a case of a patient with multiple predisposing risk factors, including a history of depression, personality disorder traits, and cannabis use, who experienced a psychotic episode with catatonic features and suicidality after several months of heavy psilocybin use. A review of similar previously published case reports demonstrates a pattern of psilocybin-induced psychosis occurring primarily in individuals with predisposing factors who have consumed either high or repeated doses of the drug. This case report furthers this pattern, which serves as both a warning that psilocybin use is not without risks and reassurance for researchers using much lower doses to treat mental illness.