Safety and tolerability of psilocybin-assisted physiotherapy in healthy volunteers

This feasibility and pilot study will assess the safety and tolerability of performing basic movement tasks (prescribed by a physiotherapist) following administration of psilocybin in healthy volunteers. The findings from this study will be used to guide the dosage of psilocybin in the companion study (‘Psilocybin-assisted therapy for refractory Functional Neurological Disorder’). 12 healthy participants will be recruited on a volunteer basis for this study. Each participant will receive three separate doses of psilocybin (5mg, 10mg, 15mg or 20mg) according to a Williams study design. Six participants will receive 5, 10 & 15mg and six will receive 10, 15 & 20mg. Each dose will be randomly assigned and taken at least 1 week apart. After providing written consent to participate in the study, participants will be assessed by a physician and psychiatrist to ensure study eligibility criteria is satisfied. If eligible, a preparation session facilitated by a mental health professional (for example, a psychiatrist or psychologist) will occur approximately one week before the participant’s first psilocybin dosing session. This will take place in dedicated room at the Austin Hospital where the dosing sessions will occur. The preparation session will consist of a discussion about drug administration, the psychoactive effects of psilocybin, and a trial of the movement tasks that will be performed during each dosing session (see below). Participants will be encouraged to raise any queries or concerns they have about the study which will be addressed by the mental health professional. On the day of psilocybin administration, the participant will arrive approximately 1 hour before dosing so trial staff can re-confirm their eligibility (including review of medication status), and record baseline vital sign measurements (heart rate, blood pressure, pulse oximetry). Psilocybin will be administered orally (capsule form) with a glass of water under the supervision of trial staff. Vital signs will be checked at hourly intervals up to 5 hours after dosing. Throughout each dosing session, participants will be asked to complete a series of movement tasks adapted from the De Morton Mobility Index and the Physio4FMD randomised controlled trial (de Morton NA, Davidson M, Keating JL, 2008; Nielsen G, et al., 2019). The trial physiotherapist will assess the participant’s ability to complete each task following an assessment form created by the researchers for the purposes of this study. At the end of each dosing session, the participant will be provided an opportunity to debrief with trial staff about their experiences, including adverse events. They will also be contacted by trial staff the following morning to assess for delayed side effects/adverse events since leaving the hospital. In addition, participants will be asked to complete a resting state fMRI brain scan prior to their first and second dose of psilocybin (baseline and follow-up scans respectively).