Yale Program for Psychedelic Science (YPPS) Manual for Psilocybin Combined with Non-Directive Support in the Treatment of OCD

The Yale Program for Psychedelic Science (YPPS) supports a multi-disciplinary research community dedicated to investigating the effects of psychedelic substances on brain function, cognition, and behavior, including their therapeutic potential in treating neuropsychiatric conditions. In support of this mission, YPPS is testing the safety and efficacy of psilocybin, administered in conjunction with non-directive psychological support, as a treatment for certain neurological and psychiatric conditions. The current study, “Effects of repeated dosing of psilocybin on obsessive-compulsive disorder: A randomized, waitlist-controlled study” (NCT05370911), will investigate the effects of repeated dosing of oral psilocybin on obsessive-compulsive disorder (OCD) symptomatology and assess psychological mechanisms that may mediate psilocybin’s therapeutic effects on OCD. The study will employ a randomized, waitlist-controlled design with blinded ratings, with participants randomized to receive either immediate treatment (two doses of oral psilocybin separated by one week) or delayed treatment (7 weeks post-randomization). An adaptive dose selection strategy will be implemented; the first dose will be fixed at 25 mg of psilocybin, and the second dose will be 25 mg or 30 mg, depending on whether or not a clinically significant response is detected after the first dose. This manual provides background and details for facilitator-related activities at various phases - pre-dosing preparation sessions, dosing sessions, and post-dosing integration sessions. The approach for psychological support by facilitators is unstructured and non-directive. In other words, facilitators do not provide any structured therapy, but rather collaborate and support participants as they prepare for psilocybin dosing sessions, ensure their psychological safety during dosing sessions, and provide them with an unstructured, non-directive context in which to process and consolidate their experiences during and after each dosing at defined time points. In doing so, while no structured therapy program is implemented, the presence and accompaniment by facilitators throughout all study sessions in the treatment phase may be experienced as supportive or even therapeutic by participants. This manual shares several features with a previous YPPS protocol-specific session monitor manual for single-dose psilocybin paired with psychological support for OCD (Ching et al., 2022), including the primary focus on a non-directive approach for preparatory, dosing, and integration sessions. Distinctive additions in this manual include a discussion of psychological processes in OCD that serve as a context for responsive facilitation of study visits, as well as updated facilitator checklists for preparatory, dosing, and integration sessions specific to the current two-dose protocol.