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
Maya Seale
Research Square July 2, 2026 preprint DOI: 10.21203/rs.3.rs-10208910/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional secondary analysis |
|---|---|
| Sample size | 210,392 |
| Population | U.S. adults in pooled NSDUH 2015–2019 data |
| Topics | MDMA Psilocybin |
| Key findings | Most sexual-identity-by-substance interactions were null, and none survived false-discovery-rate correction, so the authors conclude the data provide little support for the minorities' diminished psychedelic returns framework as applied to sexual identity. Two psilocybin-by-bisexual signals (past-year suicidal ideation and severe past-year MDE) are described as hypothesis-generating at most; psilocybin was associated with reduced severe past-year MDE among heterosexual respondents (aOR 0.85) but not bisexual respondents. |
Abstract
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.
Comparable studies
Other cross-sectional and survey studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences Individuals who had consumed psilocybin mushrooms and experienced a psychologically... | 2016 | Cross-sectional survey | n = 1,993 |
| The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms Internet survey respondents reporting challenging experiences with psilocybin | 2016 | Questionnaire development and validation | |
| Psychedelics and Mental Health: A Population Study Adult population in the United States | 2013 | Cross-sectional survey | n = 130,152 |
| Cessation and reduction in alcohol consumption and misuse after psychedelic use Individuals with prior alcohol use disorder who reported cessation or reduction in... | 2019 | Cross-sectional survey | n = 343 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |