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Naturalistic psychedelic use and changes in depressive symptoms.

Otto Simonsson, Peter S. Hendricks, Caroline M. Swords, Walter Osika, Simon B. Goldberg

Journal of Affective Disorders July 9, 2025 DOI: 10.1016/j.jad.2025.119857 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort study Peer reviewed
Sample size 12,345
Population US residents aged 18-50
Duration Study period between T1 and T2 surveys
Topics Depression
Keywords Increased depressive symptoms Negative outcomes Adverse effects Psychological well-being Preparation Risk context Lack of support Mindset
Citations 8
Key findings Naturalistic psychedelic use in a risk context was associated with moderate increases in depressive symptoms, mediated by more challenging psychedelic experiences.

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.

Comparable studies

Other observational and cohort studies on depression, most cited first.

Study Year Design Participants
Metacognitive awareness and prevention of relapse in depression: Empirical evidence. Residually depressed patients and nondepressed controls; recovered depressed patients 2002 Observational cohort with intervention components
Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Patients with treatment-resistant depression 2017 Observational cohort n = 19
Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report Patients with a depressive disorder 2015 Observational study
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59

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Depression Psychedelic-assisted therapy