RationaleResearch on psychedelics has recently shown promising results in the treatment of various psychiatric disorders, but relatively little remains known about the psychiatric risks associated with naturalistic use of psychedelics.ObjectiveThe objective of the current study was to investigate associations between naturalistic psychedelic use and psychiatric risks.MethodsUsing a sample representative of the US adult population with regard to sex, age, and ethnicity (N=2822), this study investigated associations between lifetime naturalistic psychedelic use, lifetime unusual visual experiences, and past 2-week psychotic symptoms.ResultsAmong respondents who reported lifetime psychedelic use (n=613), 1.3% reported having been told by a doctor or other medical professional that they had hallucinogen persisting perception disorder. In covariate-adjusted linear regression models, lifetime psychedelic use was associated with more unusual visual experiences at any point across the lifetime, but no association was observed between lifetime psychedelic use and past 2-week psychotic symptoms. There was an interaction between lifetime psychedelic use and family (but not personal) history of psychotic or bipolar disorders on past 2-week psychotic symptoms such that psychotic symptoms were highest among respondents who reported lifetime psychedelic use and a family history of psychotic or bipolar disorders and lowest among those who reported lifetime psychedelic use and no family history of psychotic or bipolar disorders.ConclusionsAlthough the results in this study should be interpreted with caution, the findings suggest that lifetime naturalistic use of psychedelics might be associated with more unusual visual experiences across the lifetime, as well as more psychotic symptoms in the past 2 weeks for individuals with a family history of psychotic or bipolar disorders and the reverse for those without such a family history. Future research should distinguish between different psychotic and bipolar disorders and should also utilize other research designs (e.g., longitudinal) and variables (e.g., polygenic risk scores) to better understand potential cause-and-effect relationships.