Psychedelics have been linked to improvements in depression, anxiety, and overall well-being in clinical trials and cross-sectional research [1-3]. Psychedelic use has also been linked to improvements in mindfulness [4,5], leading researchers to hypothesize that the link between psychedelic use and improvements in well-being may be driven in part by increased mindfulness [4,6,7]. Yet, there is a dearth of studies that directly explore this research domain.

This study uses a prospective data set of individuals who recently used psychedelics to examine, a priori, whether changes in mindfulness are linked to subsequent improvements in well-being, depression, and anxiety. Additionally, this study builds upon and addresses the core limitations of Mans et al [8], which found that psychedelic use was linked to improvements in mindfulness and well-being in the aforementioned data set. As Mans et al [8] did not control for major demographic and substance use confounds, include anxiety as an outcome in the analyses, nor assess how changes in mindfulness may potentially drive subsequent improvements in mental health, we aim to address these critical limitations within this study.

Table 1 presents the demographics of our participants. Table 2 presents the results of our regression models. Changes in mindfulness (T1→T4) were associated with changes in overall well-being, depression, and anxiety (T1→T5). R² values ranged from 0.19 to 0.35, indicating moderate to strong effect sizes for our models. Multimedia Appendix 1 includes supplementary robustness analyses that assess the inverse relationship between well-being and mindfulness (ie, are changes in well-being from T1→T4 associated with changes in mindfulness from T1→T5?). Although these associations were significant, R² values for these models were lower than those for our main models assessing the relationship between mindfulness changes (T1→T4) and well-being changes (T1→T5; R² range 0.11-0.17). Thus, these additional results offer further evidence supporting the notion that mindfulness changes drove well-being changes in this study.

Using a sample of individuals who recently used psychedelics, this study demonstrated that changes in mindfulness (T1→T4) were significantly associated with subsequent changes in mental well-being (T1→T5) [8]. Furthermore, models assessing the inverse associations between well-being and mindfulness (ie, assessing whether changes in well-being [T1→T4] predicted subsequent changes in mindfulness [T1→T5]) were weaker, strengthening the possibility that mindfulness drove improvements in well-being in this study.

Hill’s criteria for causation provide guidelines for evaluating the causal power of our results [10]. This study fulfills 7 of the 9 criteria: adequate strength of association, consistency with prior findings, specificity, plausibility, coherence (ie, biological plausibility), analogy (ie, comparability to related phenomena), and temporality (ie, the cause occurring before the effect). Additional research is needed to address the remaining criteria: biological gradient (ie, dose-response) and experimental evidence.

Limitations include the lack of a control group and the likelihood of bidirectional influence between changes in well-being and changes in mindfulness, both of which limit our ability to make definitive causal claims within this study. Another core limitation is our inability to control for important demographic factors in this study (eg, race/ethnicity, income, marital status). Future longitudinal studies and randomized trials can address these limitations. Overall, this study provides preliminary evidence that mindfulness may be a potential driver of the link between psychedelic use and salutary mental health outcomes.