BackgroundPsilocybin (a psychoactive compound found in “magic mushrooms” or “shrooms”) has been gaining increased attention in research and popular culture as a number of clinical and observational studies have demonstrated that it may have potential for improving mental wellbeing. Relatedly, there has been a substantial uptick in naturalistic (e.g., real-world, non-clinical) psilocybin use in the United States. While a number of longitudinal studies have demonstrated that naturalistic psilocybin use is linked to positive mental health outcomes on average, few studies have examined how the effects of psilocybin and contexts for psilocybin use may differ for White populations compared to Populations of Color. ObjectiveTo examine differences in health outcomes, subjective effects, and contexts of naturalistic psilocybin use in White participants compared to Participants of Color. MethodsThis study used data from a large, online longitudinal study of individuals who planned to engage in naturalistic psilocybin use (N = 2833). We used mixed-effects models to assess whether race/ethnicity (White vs. Participant of Color) moderated associations between time (Time 2 [initial assessment point for longitudinal measures], Time 5 [2–4 weeks post-psilocybin experience, and Time 6 [2–3 months post-experience]) and outcomes related to mental health (depression, anxiety, spiritual wellbeing, cognitive flexibility, emotion regulation [expressive suppression + cognitive reappraisal]). We also used exploratory chi-squared tests to examine differences in contexts for psilocybin use as well as differences in subjective effects related to the psilocybin experience. ResultsRace/ethnicity moderated the associations between time for predicting spiritual wellbeing (beta = −1.8; 95 % CI [−3.4, −0.17]; p < 0.05), cognitive flexibility (beta = −1.5 [−2.7, −0.26]; p < 0.05), and emotion regulation – expressive suppression (beta = 0.25 [0.06, 0.44]; p < 0.05) at Time 6 (but not Time 5). Additionally, Participants of Color reported minor differences in subjective effects and context for use compared to White participants (e.g., more likely to have set an intention prior to use, report time speeding up during the experience, etc.). We found reductions in anxiety and depression for both Participants of Color and White participants, and our moderation tests for these outcomes were not significant. ConclusionRace/ethnicity impacts the associations between psilocybin use and various markers of mental wellbeing. Future longitudinal studies and experimental studies with larger samples of color can further elucidate the preliminary findings from this study.