Psilocybin Outside the Clinic

Importance Psilocybin use has surged in the US following decriminalization efforts and promising clinical trial results. Mirroring early cannabis legalization, public access and enthusiasm are outpacing regulatory oversight and scientific understanding, posing potential risks to public health. Objective To review emerging evidence on the public health implications of unregulated psilocybin mushroom use, including trends in use, product variability, co-use with other substances, and age-related differences in outcomes. Evidence Review Sources included peer-reviewed articles, national surveillance data (eg, poison control center reports), and publicly available chemical testing data from decriminalized jurisdictions. The review emphasizes epidemiological and pharmacological findings published between January 1, 2014, and December 31, 2024, with attention to parallels from cannabis legalization research. Studies were selected based on relevance to nonclinical psilocybin use, product composition, adverse outcomes, and co-use patterns. Findings Psilocybin mushroom use has sharply increased in the US, particularly among adults aged 19 to 50 years, with more than 7 million individuals reporting use in the past year. This trend has coincided with a substantial increase in poison control center calls related to psychedelics. Testing data from decriminalized regions indicate more than 20-fold variability in psilocybin potency and inconsistent levels of minor tryptamines across mushroom strains. Clinical trial data on synthetic psilocybin do not generalize to public use due to strict participant selection and controlled environments. Co-use with cannabis is common and may increase the risk of adverse events. Evidence also suggests that age may moderate both risks and benefits. Conclusions and Relevance The expanding use of unregulated psilocybin mushrooms, combined with high variability in composition and common co-use with other substances, raises urgent public health concerns. Existing clinical data are insufficient to guide harm reduction or policy. There is a pressing need to pivot from controlled efficacy trials to real-world research on psilocybin use, including public education, potency testing, and age-specific risk assessment.