Naturalistic psychedelic use and changes in depressive symptoms
This longitudinal observational study (n=12,345) of U.S. residents found that naturalistic psychedelic use (n=505, 4.1% of participants) was associated with modest increases in depressive symptoms, particularly when occurring in 'risk contexts' characterised by negative mindset and lack of psychological support, with challenging psychedelic experiences mediating this relationship and suggesting that unsupervised psychedelic use may not be generally therapeutic and could worsen depression under certain circumstances.
Authors
- Otto Simonsson
- Peter Hendricks
- Wojciech Osika
Published
Abstract
While growing evidence suggests that psychedelic-assisted therapy may have antidepressant effects in certain populations, little is known about the effects of psychedelic use on depressive symptoms in non-clinical, naturalistic settings. This observational cohort study included a large sample of US residents (18-50 years old) and longitudinally evaluated the relationships between naturalistic psychedelic use and changes in depressive symptoms. 21,990 participants completed the T1 survey and 12,345 completed the T2 survey (56.1 % retention). In total, 505 participants (i.e., 4.1 % of T2 survey completers) reported psychedelic use during the study period. The covariate-adjusted models showed a modest association between psychedelic use during the study period and increases in depressive symptoms (β = 0.12, p = .019). When disaggregated by context of use, psychedelic use in a ‘risk context’ (e.g., negative mindset prior to psychedelic experience, no psychological support present during psychedelic experience) was associated with moderate increases in depressive symptoms relative to no psychedelic use (β = 0.30, p < .001) and psychedelic use not in a ‘risk context’ (β = 0.27, p = .004). Notably, psychedelic use in a ‘risk context’ was strongly associated with having a more challenging psychedelic experience (β = 0.59, p < .001), which in turn was associated with modest increases in depressive symptoms (β = 0.16, p = .007) and accounted for the association between psychedelic use in a ‘risk context’ and increases in depressive symptoms. In conclusion, the findings suggest that naturalistic psychedelic use may not be generally therapeutic and may result in worsening depressive symptoms under certain circumstances. Future epidemiological research should further investigate factors associated with worsening depressive symptoms following naturalistic psychedelic use.
Research Summary of 'Naturalistic psychedelic use and changes in depressive symptoms'
Introduction
Growing evidence from recent randomised trials suggests that single‑dose psilocybin administered with psychotherapy can produce rapid and sustained antidepressant effects in clinical populations, and earlier studies have reported a relatively low risk of worsening depressive symptoms and other adverse events. At the same time, naturalistic use of psychedelics has increased in countries such as the United States, including among people with depressive symptoms or disorders, raising the need to understand effects outside of controlled research and clinical settings. Several longitudinal observational studies of naturalistic psychedelic use have reported reductions in depressive symptoms, but those studies often recruited self-identified advocates or planned users and lacked unexposed comparison groups, which may introduce expectancy or selection biases and limit generalisability. Simonsson and colleagues therefore used a longitudinal observational cohort design to explore associations between naturalistic psychedelic use and changes in depressive symptoms in a large sample of US residents aged 18–50. Given prior indications that contextual factors and the quality of the acute psychedelic experience may shape outcomes, the study included additional exploratory analyses examining psychedelic use in a constructed 'risk context', the severity of challenging psychedelic experiences, and how these relate to changes in depressive symptoms over a two‑month follow‑up period.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Simonsson, O., Hendricks, P. S., Swords, C. M., Osika, W., & Goldberg, S. B. (2025). Naturalistic psychedelic use and changes in depressive symptoms. Journal of Affective Disorders, 390, 119857. https://doi.org/10.1016/j.jad.2025.119857
References (12)
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Show all 12 referencesShow fewer
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