Treatment of Persisting Symptoms After Concussion With Psilocybin Assisted Therapy (PatACT)

December 22, 2025 updated by: University of Calgary

A Randomized Double-blinded Controlled Trial for the Treatment of Persisting Symptoms After Concussion With Psilocybin-assisted Therapy: A Safety and Feasibility Trial

The goal of this randomized controlled trial is to evaluate the safety, feasibility, and efficacy of psilocybin assisted therapy as an intervention to reduce symptom burden in adult patients (aged 18-65) 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 psilocybin-assisted psychotherapy to an active control for patients with PSaC.

AIM 2: To evaluate the efficacy of an active psilocybin-assisted psychotherapy compared to an active control as a treatment for PSaC.

Participants will be asked to:

  • Complete a 2-part screening process
  • Attend a baseline assessment
  • Complete a psychoeducation preparation session(s)
  • Attend psilocybin administration session (receive high dose [25mg] or low dose psilocybin [1mg])
  • Complete 5 weekly sessions of Acceptance and commitment therapy (ACT)
  • Repeat outcome measures at 1-week, 4 weeks, 3 months, and 6 months post-psilocybin administration (online only at 6 months).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Recruiting
        • University of Calgary
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

  • Individuals of all sexes, gender identities, and ethnicities
  • Ages 18 to 65 years at the time of screening
  • Diagnosis of concussion based on the 2024 ACRM criteria
  • Meet ICD-10 criteria for PSaC for at least 3-months to a maximum of 5 years
  • Have an overall RPQ score ≥ 13 with 3 or more symptoms scored ≥3
  • Limited lifetime use of serotonergic hallucinogens
  • Ability to read/write English

An individual who meets any of the following criteria will be excluded from participation in this study:

  • Severe or moderate substance use disorder other than nicotine in past 6 months
  • Lifetime diagnosis of schizophrenia or bipolar disorders (or first or second-degree relative)
  • Active suicidal ideation or serious attempt within the past 1 year.
  • Current pregnancy or nursing, trying to become pregnant
  • Any notable abnormality on ECG or routine medical blood laboratory test
  • Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
  • Epilepsy with a history of seizures
  • Current or recent (within 12 weeks) participation in a clinical trial
  • Cognitive impairment (SLUMS score <20)
  • Suffered a moderate/severe TBI at least once in lifetime
  • Any other circumstances that, in the opinion of the investigators, compromises participant safety

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High dose (25mg)
High Dose (25mg) PEX010 (Oral Psilocybin), 25mg; single dose (20 participants) administered 24hrs prior to first ACT session
Drug: Psilocybin
See treatment arm description.
Other Names:
  • PEX010
  • magic mushrooms
Active Comparator: Low dose (1mg)
Low Dose (1mg) PEX010 (Oral Psilocybin), 1mg; single dose (20 participants)administered 24hrs prior to first ACT session
Drug: Psilocybin
See treatment arm description.
Other Names:
  • PEX010
  • magic mushrooms

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Study protocol feasibility
Time Frame: Screening, enrolment, intervention, and participation up to study end point (6-months)
The feasibility will be determined based on recruitment (greater than 30% of those screened eligible), attendance (70% intervention appointment attendance), retention (70% complete study protocol)
Screening, enrolment, intervention, and participation up to study end point (6-months)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: Throughout study completion, an average of 6 months
Safety will be determined based on adverse reactions and symptom reporting (categorized as mild, moderate, and severe)
Throughout study completion, an average of 6 months
Study protocol efficacy
Time Frame: Throughout study completion, an average of 6 months
The primary efficacy outcome is the Rivermead Post-Concussion Symptoms Questionnaire (RPQ).The RPQ assesses the severity of 16 commonly experienced PSaC symptoms using a scale of 0 ("not experienced") to 4 ("severe problem"), with higher scores indicating greater PSaC symptom burden.
Throughout study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Asberg Depression Rating Scale Self report (MADRS-S)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
The MADRS is a 10-item assessment of depressive symptoms using a recall period of the past 7 days. Total scores range from 0-60, with higher scores indicating greater depression.
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).
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
The GAD-7 is a 7-item tool which assess anxiety. Individuals rate how often they have been bothered by seven listed problems and score their responses from 0 ("not at all") to 3 ("nearly every day"). Total scores for anxiety severity are: 0-4: minimal anxiety; 5-9: mild; 10-14: moderate; 15-21: severe anxiety.
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)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
During the SCQ-initial, participants use the timeframe of the 6-months prior to the concussion, and since the concussion. The SCQ-follow-up will have a recall period of since the most recent SCQ was completed. Total scores of 0-7 indicate no clinically significant change; 8-15: subclinical change; 16-22: clinical changes of moderate severity; 23-36: clinically severe changes in sleep or wakefulness.
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).
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
This 6-item tool assesses how headache intensity impacts daily life functioning. Headache intensity and frequency are measured from "never" to "always", with greater scores indicating greater impact on daily life function due to headache. Total scores of 49 or less indicate headaches have little to no impact on daily life; 50-55: headaches have some impact on life; 56-59: headaches have substantial impact on life; 60 or more: headaches have severe impact on life.
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)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
A 25-item self-reported questionnaire which assesses the impact of dizziness on daily life. Scores from functional, emotional, and physical domains are summed to give a score between 0-100 with greater scores indicating greater impact.
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)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
A 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Greater symptom scores indicate greater symptom burden
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)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
This questionnaire measures health-related quality of life specific to individuals after traumatic brain injury. Covers six domains of health-related quality of life (cognition, self, daily life and autonomy, social relationships, emotions, and physical problems) to provide an overall score, with higher scores indicating greater quality of life.
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)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
A 36-item self-report scale designed to assess multiple aspects of emotion dysregulation. Six subscale scores and a total score are calculated.
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
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]
The Thinking Aloud Task (TAT) measures cognitive flexibility in relation to thought dynamics, tapping into the speed and expansiveness of thoughts, which relate to real-time emotion regulation and overall social and emotional well-being.
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
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]
The Probabilistic Reversal Learning (PRL) task is a measure of reward-related cognitive flexibility that requires participants to choose a shape that fits an inferred rule and adapt behavior once rules switch
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)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
A 7-item questionnaire measuring psychological flexibility. Scores range from 0 to 49 with higher scores indicating greater psychological flexibility
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)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
A 7-item questionnaire which measures psychological flexibility about the thoughts and feelings related to brain injury. Scored on a 5-point Likert scale, scores range from 0-36 with higher scores indicating greater psychological flexibility
Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
Cognitive Fusion Questionnaire (CFQ-7)
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
A 7-point Likert scale measuring cognitive fusion. Scores range from 0 to 49 with higher scores indicating greater fusion with one's thoughts.
Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
Bergs Card Sorting Task
Time Frame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]
Cognitive flexibility task - Participants must select the stimulus that is different from others based on feedback and adapt their responses once the criteria for correct choice switches. Perseverative errors are defined as the number of instances in which three incorrect responses are made based on a previous rule, and they are thought to reflect less cognitive flexibility (or cognitive rigidity)
Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Calgary

Collaborators

University of British Columbia

Investigators

  • Principal Investigator: Chantel T Debert, MD MSc FRCPC, University of Calgary

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 27, 2025

Primary Completion (Estimated)

October 30, 2026

Study Completion (Estimated)

March 30, 2027

Study Registration Dates

First Submitted

September 11, 2024

First Submitted That Met QC Criteria

September 23, 2024

First Posted (Actual)

September 27, 2024

Study Record Updates

Last Update Posted (Actual)

December 30, 2025

Last Update Submitted That Met QC Criteria

December 22, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REB24-0334

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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