Effects of Repeated Psilocybin Dosing in OCD

Aim 1: To examine the effects of two doses of psilocybin on OCD symptoms among participants in the immediate treatment condition, compared to participants in the waitlist control/delayed treatment condition. The investigators hypothesize that participants in the immediate treatment group will report statistically significantly greater symptom improvement from baseline 4 days post-second dose, compared to participants in the waitlist control/delayed treatment group at the same interval during their waitlist phase. Aim 2: To examine the effects of two doses of psilocybin on OCD symptoms, compared to one dose. The investigators hypothesize that two doses of oral psilocybin will reduce OCD symptoms to a statistically significantly greater extent than one dose. This study aims to investigate the effects of repeated dosing of oral psilocybin on OCD symptomatology and assess psychological mechanisms that may mediate psilocybin's therapeutic effects on OCD. This study will employ a randomized, waitlist-controlled design with blinded independent ratings, with participants randomized to receive either immediate treatment (two doses oral psilocybin separated by one week) or delayed treatment (7 weeks post-randomization). An adaptive dose selection strategy will be implemented, with the first dose being standardized at 25 mg of psilocybin, and the second dose being either the same or a higher dosage (i.e., 30 mg) on the basis of a clinically significant response from baseline or not, respectively, 4 days post-first dose. This study is conducted entirely on an outpatient basis with the possibility of remote/virtual follow-up visits after each dosing session. The dosing sessions last the entire day, and participants will be medically cleared prior to being permitted to return home with assistance (e.g., driven by a family member or friend, or ride share).