The role of Oceanic boundlessness in psilocybin-assisted therapy in patients with treatment-resistant depression: Exploring its relationship with connectedness to nature.

Psilocybin (4-phosphoryloxyl-N,N-dimethyltryptamine), a natural tryptamine occurring in psilocybe mushrooms, has shown promise in treating a range of mental health conditions, including major depressive disorder (MDD), depression and anxiety in advanced-stage cancer, and alcohol use disorder. There is preliminary evidence from both non-clinical surveys of naturalistic psychedelic use and clinical trials of psilocybin therapy showing that oceanic boundlessness (OCB) is a key part of the psychedelic experience correlated with greater reductions in depression symptoms (Roseman et al., 2017). Additionally, research indicates that psychedelic experiences reliably enhance individuals' connectedness to nature, with effects evident beyond the acute state and across both clinical and naturalistic contexts (Forstmann et al., 2023; Kettner et al., 2019; Lyons & Carhart-Harris, 2018). The Psilocybin in Depression Resistant to standard treatments (PsiDeR) trial was a two arm, double-blind, randomised, placebo-controlled phase 2 trial evaluating feasibility and safety of 25mg psilocybin versus placebo in adults with treatment-resistant depression (TRD). The aim of this secondary data analysis is to confirm reports that OCB is correlated with greater reductions in depression symptoms and extend our understanding of the key role of OCB in PAP by investigating whether OCB also mediates increases in connectedness to nature. This will help deepen our phenomenological understanding of OCB and further establish it as a central psychological mechanism of PAP. Moreover, given the established mental-health benefits of increased connectedness to nature, this research may help inform the development of approaches that support and reinforce this domain of the unitive experience, which may help to amplify and sustain the reductions in depressive symptoms associated with OCB.