Journal of Humanistic Psychology, Ahead of Print. A resurgence of research has begun to systematically examine the relationship between psychedelic use and mental health and well-being. Although preliminary findings examining the therapeutic value of these substances show promise, the mechanisms through which psychedelic use may predict reduced mental distress remain poorly understood. To this end, we surveyed a community sample of individuals (n = 159) who endorsed lifetime psychedelic use to examine relationships among psychedelic use and self-reported spirituality, difficulties in emotion regulation, and symptoms of mental health issues. Results revealed a pathway through which classic psychedelic use predicted greater spirituality, which in turn predicted better emotion regulation, ultimately predicting lower levels of anxiety, depressed mood, and disordered eating. These results contribute to our understanding of potential mechanisms of change with respect to psychedelics and mental health. They also add to the growing body of literature pointing to the healing effects of the cultivation of spirituality and emotion regulation as separate and related constructs.