Overall, psilocybin is safe, well tolerated, and has few adverse effects or interactions. MAOIs are the main exception because they can inhibit MAO-A, a secondary metabolic route, and potentially cause serotonin toxicity. Most psychotropic medications can attenuate psilocybin’s effects, and benzodiazepines are the preferred option for managing anxiety during psilocybin experiences in controlled clinical settings.12 Of all interactions, psilocybin’s pharmacological contraindication with lithium is the most clinically relevant due to the risk of seizures and other serious adverse events.11 Clinicians need to monitor vital signs and other physical effects on a case-by-case basis.
It's important for clinicians to become familiar with psilocybin’s pharmacological interactions because the drug has been legalized in some states for supervised or regulated therapeutic use and is advancing toward FDA approval and DEA rescheduling. Many individuals in the community are also seeking psilocybin experiences to manage symptoms, for therapy, or for personal growth.