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.
Abstract of Naturalistic psychedelic use and changes in depressive symptoms
“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.“
Authors: Otto Simonsson, Peter S. Hendricks, Caroline M. Swords, Walter Osika & Simon B. Goldberg
Summary of Naturalistic psychedelic use and changes in depressive symptoms
Recent advances in psychedelic-assisted therapy, particularly in controlled clinical trials involving substances like psilocybin, have shown promising antidepressant effects. These interventions often involve structured environments, professional support, and psychological preparation, leading to positive outcomes with minimal adverse effects. However, this clinical success has contributed to an increase in unsupervised, naturalistic psychedelic use in the general population, particularly in the United States, where individuals with depressive symptoms may turn to psychedelics outside clinical oversight.
Although some longitudinal observational studies suggest naturalistic psychedelic use can lead to improvements in depressive symptoms, there are important methodological concerns. Many of these studies attract participants who already support psychedelic use or plan to take psychedelics, which may introduce bias. Additionally, the lack of comparison groups (people who do not use psychedelics) limits conclusions about effectiveness. These issues complicate the interpretation of the findings and reduce the ability to generalise the outcomes to broader public health contexts.
The authors aimed to address these limitations through a large-scale, observational cohort study. They explored how naturalistic psychedelic use, particularly within different use contexts, was associated with changes in depressive symptoms over time. They focused on the influence of “risk context”—a term denoting situations where psychedelic use is more likely to be psychologically harmful (e.g., absence of support or a negative mindset). The study also examined whether challenging experiences during a psychedelic session explained increases in depressive symptoms.
Methods
Procedures
Find this paper
Naturalistic psychedelic use and changes in depressive symptoms
https://doi.org/10.1016/j.jad.2025.119857
Open Access | Google Scholar | Backup | 🕊
Cite this paper (APA)
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, 119857.
Study details
Compounds studied
MDMA
Psilocybin
LSD
DMT
Ayahuasca
Mescaline
Topics studied
Depression
Healthy Subjects
Study characteristics
Longitudinal
Survey
Participants
12345
Humans