Sexual identity as a moderator of associations between lifetime MDMA/ecstasy or psilocybin use and mental health outcomes: An exploratory analysis of a nationally representative sample using NSDUH 2015-2019

Abstract Purpose Lifetime MDMA/ecstasy and psilocybin use have been associated with lower odds of psychological distress, suicidality, and depressive episodes, but these associations may vary by marginalized identity. Building on minorities' diminished psychedelic returns (MDPR) framework and extending Jones and Nock's race/ethnicity moderation work, this study tests whether sexual identity moderates them. Methods This cross-sectional secondary analysis used pooled NSDUH 2015-2019 data (N = 210,392 adults). Survey-weighted logistic regressions tested whether sexual identity moderated associations between lifetime MDMA/ecstasy or psilocybin use and six mental health outcomes. In a two-step exploratory design, full-sample interactions were screened first, with subgroup models tested only for substance-outcome combinations showing significant moderation (p ≤.05). Results Lifetime MDMA/ecstasy and psilocybin use were more common among bisexual and lesbian/gay than heterosexual respondents. Bisexual identity moderated psilocybin associations with past-year suicidal ideation (p =.03579) and severe past-year major depressive episode (MDE; p =.04950); no other interactions were significant. In subgroup models, psilocybin was associated with reduced severe past-year MDE among heterosexual (aOR = 0.85 [0.74, 0.98], p =.03170) but not bisexual respondents. No subgroups showed a psilocybin-suicidal-ideation association. Conclusion This data provides little support for MDPR as applied to sexual identity: most sexual-identity-by-substance interactions were null and none survived false-discovery-rate correction. The two psilocybin-bisexual signals are hypothesis-generating at most, but the bisexual specificity suggests differences in social and integration support may shape whether psychedelic exposure benefits mental health.