Psilocybin-assisted Therapy for Post-Traumatic Stress Disorder in Survivors of Intimate Partner Violence

The overall objective of this study is to evaluate the efficacy of psilocybin administered with Acceptance and Commitment Therapy (ACT) as an intervention to reduce post-traumatic stress disorder (PTSD) symptom burden in survivors of intimate partner violence (IPV).

This trail will test the following 2 aims:

AIM 1 : To compare the efficacy of a therapeutic psilocybin dose (25mg) at improving outcomes on the PCL-5 and CAPS-5 as compared to an active control psilocybin dose (1mg) (allocation ratio 1:1) in IPV survivors with chronic PTSD. Mean baseline scores will be compared to scores at each follow-up timepoint (1-week, 4 weeks, 3 months (PCL-5 only), and 6 months post-psilocybin administration).

AIM 2: to evaluate the efficacy of psilocybin on quality of life, cognitive function, motor ability, depression, anxiety, and cognitive flexibility. Mean baseline scores will be compared to scores at each follow-up timepoint (1-week, 4 weeks, 3 months (online only), and 6 months post-psilocybin administration).

The secondary efficacy outcomes will include measures of mood, anxiety, post-traumatic stress, cognitive flexibility, emotional regulation, and quality of life.

Exploratory Aim: Exploratory objectives of this study include evaluating blood biomarkers reflective of inflammation, growth factors, brain injury, and oxidative stress relevant to PTSD and psilocybin's mechanisms of action.

A total of 76 male and female patients between the ages of 18-65 with the last incident of IPV greater than 6 months prior with a score of 1 on the Composite Abuse Scale with repetition of abusive events, meeting DSM-5 criteria for PTSD and a minimum PCL-5 score of 33.

All patients will undergo a thorough, 2-part screening procedure. Eligible participants will be randomly allocated 1:1 to either the high dose (38 participants) or low dose (38 participants) psilocybin groups. All participants will be asked to attend a baseline session consisting of clinical and behavioural outcome measures followed by a pre-dosing psychoeducation session. Following the single dosing session, participants will complete 5-6 weekly ACT sessions. Outcome measure assessments will be repeated at 1-week, 4 weeks, 3 months (online only), and 6 months post-dosing.

• Montgomery-Åsberg Depression Rating Scale, Self-Reported (MADRS-S) [Time frame: Change from baseline to 1-week, 4 weeks, 3 months, and 6 months post-dosing]
• Generalized Anxiety Disorder-7 (GAD-7) [Time frame: Change from baseline to 1-week, 4 weeks, and 3 months, and 6 months post-dosing]
• Rivermead Post-Concussion Symptoms Questionnaire (RPQ) [Time frame: Change from baseline to 1-week, 4 weeks, and 3 months, and 6 months post-dosing]
• The Acceptance and Action Questionnaire II (AAQ-II) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]
• Cognitive Fusion Questionnaire (CFQ-7) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]
• The World Health Organization Disability Assessment Schedule 2.0 12-item survey (WHODAS) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]
• 9. EuroQol-5D (EQ-5D-5L) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]
• Cognitive Flexibility Scale (CFS) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]
• The Pittsburgh Sleep Quality Index (PSI) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]
• The Trail-Making Test (TMT) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]
• The Digit Span Task (DS) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]
• The Berg's Card Sorting Task (BCST) [Time frame: Change from baseline to 1-week, 4 weeks, and 6 months post-dosing]