Adverse reactions to psychedelics in naturalistic settings are associated with current psychopathology and well-being: A correlational study

Most acute adverse reactions were associated with greater current psychopathology and lower well-being, whereas vomiting showed the opposite pattern.

Rojas-Hernández et al. (2026) surveyed 1,022 people reporting naturalistic psychedelic use and found that acute adverse reactions were generally associated with similar delayed adverse experiences, higher current psychopathology and lower psychological well-being; vomiting showed a different pattern.

Adverse reactions were also associated with contextual factors, motivations for use and patterns of substance use, while younger age and more frequent current psychedelic consumption were associated with greater odds of reporting adverse reactions.

Lifetime MDMA use was additionally associated with poorer current psychological indicators. However, the study was cross-sectional and retrospective, and adverse reactions were not linked to specific substances or individual episodes of use, so the findings demonstrate associations rather than causation and cannot establish which substances or circumstances caused particular outcomes. The authors conclude that prospective research is needed to clarify these relationships and inform harm-reduction strategies

Abstract

This study examines acute and delayed adverse reactions reported in naturalistic psychedelic use, focusing on their associations with substance-use patterns, contextual variables, and user motivations. Using an online survey incorporating the Psychedelic Use Scale, data were collected from a large naturalistic sample (N = 1022) to analyze patterns of self-reported adverse reactions. Acute adverse reactions were consistently associated with similar delayed adverse reactions, suggesting continuity between immediate and subsequent self-reported adverse experiences. Furthermore, most acute adverse reactions, with the exception of vomiting, which showed an opposite pattern, were associated with higher current psychopathology and lower well-being.

Self-reported lifetime use of individual psychedelics (e.g., DMT, MDMA, and LSD) and combined substances (e.g., alcohol, caffeine, and cannabis) showed participant-level associations with specific self-reported adverse-reaction categories, while MDMA use was also associated with poorer current psychological indicators. Adverse reactions were also associated with contextual variables, including setting, type of companionship, and user motivations. Younger age and higher current frequency of psychedelic consumption were associated with higher odds of reporting adverse reactions.

Because the study is cross-sectional and retrospective, and adverse reactions were not linked to specific substances or psychedelic episodes, the findings should be interpreted as correlational, hypothesis-generating co-reporting patterns rather than as substance-specific attribution. Nevertheless, they provide an empirical basis for future prospective, longitudinal, and clinical studies aimed at clarifying temporal relationships and informing harm reduction strategies.

Rojas-Hernández, J., Borkel, L.F., Santana del Pino, Á., Quintana-Hernández, D.J. and Henríquez-Hernández, L.A. (2026). Adverse reactions to psychedelics in naturalistic settings are associated with current psychopathology and well-being: A correlational study. Psychiatry Research, 367, 117516. Read Paper

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