Knowledge Synthesis in the Science of Psilocybin: Scoping Reviews of Clinical and Preclinical Research

Abstract

Psilocybin is a psychedelic compound of interest to clinicians, researchers and the general public for its unique effects on perception, cognition and emotion. Fifteen years of clinical trials, reviewed here using the scoping review method of knowledge synthesis , provide evidence for the safety and therapeutic efficacy of psilocybin when combined with psychological supports. A similar review of more than 50 years of research on non-human animals shows the safety of psilocybin and demonstrates persisting positive effects of psilocybin on self-regulation. To provide context to these scoping reviews, I conducted a detailed literature review and a separate narrative review on the neuroscience of psilocybin, with a marked interest in the dynamics of neuroplasticity and how habits of self-regulation are formed, revised and updated. While my working hypothesis considered mystical states as the mechanism of therapeutic action underlying psilocybin’s apparent benefits, the evidence was stronger to support a revised hypothesis: that psilocybin improves self-regulation. It does so by disrupting habit, potentiating new learning and promoting improvements to health behaviours. I offer here a novel contribution to the literature: a time-based Transition State Model of Psychedelic Effect which views psilocybin as a catalyst to improved flexibility of thought and behaviour. Psilocybin appears to attenuate or loosen the effects of past conditioning which appear as habits and which have become hard-wired into brain networks. This learning model heavily weights the activities undertaken in the days and weeks following psilocybin administration, providing a basis for psilocybin-assisted therapies to leverage this critical period for improvements to health behaviours.