Identifying Optimal Responses to Challenges Related to Expanding the Perception Box in Psilocybin-Assisted Therapy

Overview:

Researchers will study the effects of psilocybin on adults with depression, using various methods to track changes in behavior and psychological states to identify factors that predict positive or negative outcomes of these perception-altering experiences.

Abstract:

Background: To better understand the complex interplay of benefits and risks that accompany transformative, Perception Box-expanding experiences, and to maximize benefits while reducing risks, this project aims to (1) characterize precursors to deterioration vs. improvement (2) identify modifiable real-world variables linked with differential outcomes of psilocybin-induced Perception Box expansion, and (3) apply these to identify when challenging experiences lead to better vs. worse outcomes.

Methods: In a trial that will administer a single 25-mg dose of psilocybin to 141 adults with Major Depressive Disorder (MDD), this study will conduct intensive, multi-modal ecological assessment of real-world social behaviors and psychological experiences during the 2 weeks prior to, and 2 weeks following, psilocybin administration. We will use complex dynamic systems modeling to compute sudden gains, losses, and their early warning signs, among study participants. Alongside traditional self-report measures of depression and wellbeing, this study will empirically observe real-world behaviors by means of the Electronically Activated Recorder (EAR), a smartphone app that records short samples of ambient sound while participants go about their daily lives. Collected at baseline and 1 and 4 weeks after dosing, these data will allow us to identify risk and resilience factors based on objectively observed behaviors and social interactions, and to explore how observed behavioral variables predict both therapeutic gains and adverse effects (AEs) after psilocybin. Ecologically momentary assessment will be collected 4x per day by means of a smartphone app for 14 days before and after dosing, including assessment of psychological states and a stream-of-consciousness voicediary. Enhanced assessment of post-acute adverse events will be conducted with the Psychedelic Assisted Therapy Adverse Events (PATAE) measure to assess cultural, spiritual, interpersonal,

psychotherapeutic, metacognitive, and perceptual domains, uniquely relevant to shifts in the Perception Box but not yet addressed elsewhere in psychedelics research. Sudden gains and losses, as well as “early warning signals” within longitudinal trajectories derived from EMA and EAR data will be identified via complex dynamic systems modeling, as well as “early warning signals.”

Broader Impact:

Finding the conditions that encourage benefits from Perception Box-expanding tools like psychedelics, while reducing the risk of deterioration, will be necessary for making psychedelics safe, effective, equitable, and beneficial, ensuring that those who experience challenges are not left behind. Because challenges can accompany other Perception Box-expanding techniques (e.g., meditation), this research will be directly relevant for research on those techniques by developing readily transferable methodological frameworks for subsequent studying the real-world impacts of Perception Box shifts.