Psilocybin-assisted psychotherapy for the treatment of depression and anxiety associated with life-threatening illness

Psilocybin assisted psychotherapy The study aim is to investigate the efficacy of psilocybin plus psychotherapy (before during and after the psilocybin dose sessions) in the treatment of depression and/or anxiety associated with having a terminal illness -Materials used - 25 mg Psilocybin (active dose) - oral capsule, single dose supervised administration with drug packaging return - 100mg Niacin (active placebo) - oral capsule, single dose supervised administration 11 sessions of psychotherapy (including two dose days) will take place across the two parts of the study Preparatory psychotherapy - 3 sessions before dose 1 Integrative/preparatory psychotherapy - 3 sessions after dose 1 and before dose 2 Integrative psychotherapy - 3 session post dose 2 Psychotherapy session frequency varies - initially, the first 3 psychotherapy sessions and dose day occur within the first 14 days of baseline and another session occurs the day following the first dose. Following this, psychotherapy occurs approximately every 3rd week until the second dose, and again every 3 weeks following the second dose - if additional sessions are required, this is arranged and documented. **There is a psychotherapy session the DAY BEFORE each dose day to ensure that the participant is adequately prepared, and another psychotherapy session the DAY AFTER the dose session to ensure the participant has an opportunity to integrate their experiences. PART 1 = RCT (Baseline - 6-7 weeks post dose one) Dose day 1 = EITHER 25mg psilocybin OR 100mg Niacin (active placebo) PART 2 = Open label (commences 6-7 weeks following dose 1 which is at the same time as the completion of the RCT arm- Participants are followed up for 26 weeks post dose 2/open label dose) Dose day 2 = Psilocybin 25mg for all participants. Follow-up continues to 26 weeks weeks post dose two. The psychotherapy component is largely informed by meaning centred psychotherapy approaches for palliative care patients, plus Johnson, Richards & Griffiths (2008) ‘Human Hallucinogen Research: Guidelines for Safety’, which incorporates safeguards and protocol guidelines to include the importance of ‘set and setting’ for participants. In addition, anxiety management strategies will be employed in preparatory sessions. Prepratory psychotherapy sessions include obtaining a developmental history and formulation, psychoeducation about potential effects of psilocybin, anxiety management and meaning centered psychotherapy. Integrative psychotherapy occurs post dose sessions and includes integrating experiences of the participant on their dose day and worked through using components of meaning centered psychotherapy. Dose days occur over several hours and are largely monitoring/supporting the participant through their experience. Integrative work may commence towards the end of the dose day but are largely confined to the sessions following the dose day (not on the dose day itself). Treatment fidelty will be monitored by use of session checklists, and audit of video/audio material obtained during sessions. PROCEDURES Post screening and upon being deemed eligible, participants are given baseline measures including a semi-structured interview, and commence preparatory psychotherapy (minimum 3 x sessions) before commencing their first psilocybin assisted psychotherapy dose day. Post the first dose day (two in total), there is further integrative psychotherapy sessions and preparation for dose two. Post dose two, integrative psychotherapy sessions are conducted. Measures assessing depression, anxiety, death anxiety, quality of life, spiritual wellbeing, demoralisation and mystical experiences (and other areas) are given throughout various time points in the study. Psychotherapy sessions will last up to 2 hrs, with the dose day lasting up to 8 hours. Clinically trained healthcare professionals (psychologists, social workers, psychiatrists) with a minimum of 3 years (average 8 yrs) experience working in psycho-oncology and palliative care are providing the psychedelic assisted psychotherapy. All clinicians have knowledge of the potential effects of psilocybin and altered states of consciousness as well as clinical parameters requiring escalation of care in the event of adverse events. All have current training in ICH-GCP. Most psychotherapy sessions will be delivered face to face but in extenuating circumstances, may be delivered by phone or internet video chat (such as Skype or zoom). All sessions are delivered individually to participants with two therapists present at all times. All psychotherapy and psilocybin dose sessions will be delivered onsite at St. Vincent’s Hospital Melbourne. The treatment room is not a usual medical consulting room, rather, a spacious room specifically designed for the trial to emulate a living room environment whereby a relaxed and comforting atmosphere is created for the participant. Participants are able to choose the music playlist that they would prefer for the psilocybin dose sessions.