Treatment of Persisting Symptoms After Concussion With Psilocybin Assisted Therapy

The overall objective of this study is to evaluate the safety, feasibility, and efficacy of psilocybin assisted therapy administered with Acceptance and Commitment Therapy (ACT) as an intervention to reduce symptom burden in patients with persisting symptoms after concussion (PSaC).

This trail will test the following 2 aims:

AIM 1 : To test the safety and feasibility of an active/high dose (25mg) psilocybin-assisted psychotherapy to an active control (1mg) for adults with PSaC. Safety will be determined through the reporting of adverse events and response following psilocybin for each participant up to 6-months. Feasibility will be determined through recruitment, enrollment, and adherence rates.

AIM 2: To evaluate the efficacy of an active/high dose (25mg) psilocybin-assisted psychotherapy compared to an active control (1mg) as a treatment for PPCS at 1-week, 4 weeks, 3 months, and 6 months post-psilocybin administration. The primary efficacy outcome will be the change in PSaC burden (RPQ).

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

A total of 40 male and female patients between the ages of 18-65 with a diagnosis of mild traumatic brain injury (American College of Rehabilitation Medicine 2023 criteria) who meet criteria for persisting symptoms after concussion (ICD-10) within 3 months to 5 years will be recruited from Calgary brain injury clinics and the community.

All patients will undergo a thorough, 2-part screening procedure. Eligible participants will be randomly allocated 1:1 to either the high dose (20 participants) or low dose (20 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 weekly ACT sessions. Outcome measure assessments will be repeated at 1-week, 4 weeks, 3 months, and 6 months post-dosing.

• Montgomery-Asberg Depression Rating Scale Self report (MADRS-S) [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• Generalized Anxiety Disorder-7 (GAD-7). [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• Sleep and Concussion Questionnaire (SCQ) [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• Headache Impact Test (HIT-6). [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• Dizziness Handicap Questionnaire (DHI) [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• PTSD Checklist for DSM-5 (PCL-5) [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• The Quality of Life after Brain Injury (QOLIBRI) [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• Difficulties in Emotion Regulation Scale (DERS) [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• Think Aloud Task [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]]
• Probabilistic Reversal Learning Task [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]]
• The Acceptance and Action Questionnaire II (AAQ-II) [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]
• The Acceptance and Action after Brain Injury Questionnaire (AAQ-ABI) [Срок оценки: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]]