Classic Psychedelic Use and Mechanisms of Mental Health: Exploring the Mediating Roles of Spirituality and Emotion Processing on Symptoms of Anxiety, Depressed Mood, and Disordered Eating in a Community Sample

Classic psychedelics are serotonin (5-HT2A) agonists such as LSD, psilocybin, mescaline and DMT (including ayahuasca). These substances produce altered perception, feelings of interconnectedness and affective introspection and have long histories of plant‑based spiritual and healing use. Recent epidemiological, qualitative, laboratory and clinical work has reopened scientific interest in their therapeutic potential, with studies reporting lower rates of psychological dysfunction among users and randomised or open‑label trials showing anxiolytic and antidepressant effects in populations such as terminally ill patients and those with treatment‑resistant depression. Despite these promising findings, the mechanisms linking psychedelic use to improved mental health remain poorly understood. Lafrance and colleagues set out to test one proposed pathway by which psychedelic use might relate to better mental health: that greater psychedelic use is associated with higher self‑reported spirituality, which in turn predicts improved emotion regulation capacity, and that improved emotion regulation then predicts lower symptoms of anxiety, depressed mood and disordered eating. The study examined these relationships in a community sample of lifetime psychedelic users and additionally considered frequency of use (as a proxy for dose) as an individual‑difference variable that might influence outcomes.

The study used a cross‑sectional, survey‑based design drawing from a larger project. Recruitment (n = 461) was via undergraduate psychology classes at two Canadian universities, Reddit forums, and Amazon Mechanical Turk; participants had to read English to participate. From this larger sample, a subset of 159 respondents who reported lifetime psychedelic use were included in the analyses reported here. Participants provided informed consent and the study received ethics approval from The University of British Columbia and Laurentian University. Compensation varied by recruitment source (course credit, payment or entry into a draw). Lifetime psychedelic use was assessed with a 5‑point Likert item (1 = never to 5 = more than 10 times), summed across five classic psychedelics (LSD, psilocybin, mescaline, DMT and ayahuasca). Spirituality was measured with the 32‑item WHOQOL‑SRPB (higher scores indicate greater spirituality/religiosity/personal beliefs). Emotion regulation difficulties were measured with the 36‑item DERS (higher scores indicate greater difficulties). Symptoms of anxiety, depressed mood and disordered eating were measured with the Beck Anxiety Inventory (BAI), the CESD‑R depression scale, and the Eating Disorders Examination Questionnaire (EDE‑Q), respectively. Typical scale ranges and directionality are reported in the extracted text. Analytically, the investigators first ran descriptive statistics and a series of regression analyses testing links in the proposed mediation chain. They then tested the full model using structural equation modelling in AMOS Graphics 20.0. Because the psychedelic use variable was highly positively skewed, it was log10‑transformed and all variables were mean‑centred prior to modelling. In the SEM the three dependent variables (anxiety, depressed mood, disordered eating) were allowed to have correlated errors, and indirect effects were estimated using bias‑corrected bootstrapping with 1,000 samples.

The analytic sample comprised 159 lifetime psychedelic users aged 18–69 (mean age 23.44, SD 7.44). Descriptively, approximately 96% (n = 152) reported past psilocybin use and about one third (n = 52) reported using more than one classic psychedelic. In simple regressions, more frequent psychedelic use predicted higher spirituality, b = 0.155, t = 1.95, p = 0.052, R2 = 0.024 (note p = 0.052 is marginally above the conventional 0.05 threshold). Higher spirituality was associated with fewer difficulties in emotion regulation: spirituality predicted DERS scores, b = -0.395, t = -5.38, p < 0.001, R2 = 0.156. Separate regressions showed that greater difficulties in emotion regulation (higher DERS) were positively associated with higher self‑reported anxiety, greater depressed mood and more disordered eating symptoms. In the structural equation model (n = 159), psychedelic use (log‑transformed) was entered as the independent variable, spirituality as mediator 1, emotion regulation (DERS) as mediator 2, and anxiety, depressed mood and disordered eating as the three outcomes. Bias‑corrected bootstrapped 95% confidence intervals (1,000 samples) indicated significant indirect effects of psychedelic use on anxiety (95% CI = [-0.08, -0.009], p = 0.015), depressed mood (95% CI = [-0.09, -0.01], p = 0.016) and disordered eating (95% CI = [-0.05, -0.005], p = 0.014). Because these confidence intervals excluded 0, the authors concluded the indirect paths were significant at p < 0.05. Direct effects of psychedelic use on each of the three outcomes were nonsignificant, consistent with a mediated rather than a direct relationship in this cross‑sectional model.

The investigators interpret their findings as preliminary evidence for a chained pathway linking psychedelic use to better mental health via increased spirituality and improved emotion regulation. More frequent lifetime psychedelic use was associated with higher self‑reported spirituality, which in turn related to fewer difficulties regulating emotion, and these improvements in emotion‑processing capacity were associated with lower symptoms of anxiety, depressed mood and disordered eating. The authors highlight that spirituality and emotional breakthrough have been identified in prior work as predictors of wellbeing following psychedelic experiences and suggest that higher doses, which tend to produce stronger peak spiritual or mystical experiences, may lead to greater gains in emotion regulation and downstream mental health. Context and set/setting are emphasised as important moderators; the authors note that therapeutic benefit of higher doses is likely contingent on psychologically supportive environments and that combining psychedelics with psychotherapy will be a key area for future research. They also frame the findings within the broader resurgence of psychedelic research, and underscore cultural and ethical considerations: psychedelics have long been used in Indigenous healing and spiritual traditions and there is a need for greater representation of those communities in contemporary research and clinical practice. Clinically, the authors argue the results point to the potential value of attending to spirituality within psychotherapy as a means to enhance emotion regulation and improve outcomes for emotion‑based disorders. They acknowledge that integrating spirituality into therapy may be unfamiliar or uncomfortable for some clinicians and call for appropriate training to ensure ethical, client‑centred practice. The discussion also reiterates methodological limitations the authors acknowledged: the cross‑sectional design precludes causal inference, the sample was relatively homogeneous and largely drawn from university recruits with predominantly low frequency use and heavy representation of psilocybin users, and reliance on self‑report introduces potential bias. The authors recommend longitudinal and experimental work, larger and more diverse samples, examination of different psychedelic substances and doses, and use of observational or behavioural measures to test the robustness and causal direction of the proposed mediation model. They additionally note an alternative interpretation consistent with their data: individuals with better distress tolerance may be more likely to use psychedelics, which would imply selection effects rather than a causal effect of psychedelic use on emotion regulation and mental health outcomes. Overall, Lafrance and colleagues present correlational evidence that spirituality and emotion regulation together may account for a portion of the relationship between classic psychedelic use and reduced symptoms of anxiety, depressed mood and disordered eating, while emphasising the preliminary nature of these findings and the need for more rigorous follow‑up research.