Treatment of Persisting Symptoms After Concussion With Psilocybin Assisted Therapy

NCT06615908 | Recruiting Phase 1 DMC

• 1 other identifier: REB24-0334
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Persisting Symptoms After Concussion

Keywords

Psychotherapy; Psilocybin; Concussion; Mild Traumatic Brain Injury; Acceptance and Commitment Therapy

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  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

  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

• Study protocol feasibility

  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)

Secondary Outcomes (14)

• Montgomery-Asberg Depression Rating Scale Self report (MADRS-S)

  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).

  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)

  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).

  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)

  Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]

Study Arms (2)

High dose (25mg)

EXPERIMENTAL

High Dose (25mg) PEX010 (Oral Psilocybin), 25mg; single dose (20 participants) administered 24hrs prior to first ACT session

Drug: Psilocybin

Low dose (1mg)

ACTIVE COMPARATOR

Low Dose (1mg) PEX010 (Oral Psilocybin), 1mg; single dose (20 participants)administered 24hrs prior to first ACT session

Drug: Psilocybin

Interventions

Psilocybin DRUG

See treatment arm description.

Also known as: magic mushrooms, PEX010

High dose (25mg); Low dose (1mg)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Calgary: lead
• University of British Columbia: collaborator

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N 2T9, Canada

RECRUITING

MeSH Terms

Conditions

Brain Concussion

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Chantel T Debert, MD MSc FRCPC

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chantel T Debert, MD MSc FRCPC

CONTACT

(403) 944-4500; cdebert@ucalgary.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The group assignments to active (25mg) and control (1mg) psilocybin-assisted therapy will be based on a blocked randomization list (10 participants per block) using sealed envelopes created by an employee of the University of Calgary, who will not be involved in the conduct, or the analysis of the study. The pharmacy administering the psilocybin will be responsible for maintaining the master randomization code list and only the technician preparing the samples will have access to the envelopes and code list. When a new study ID is generated, the technician is to verify the randomization and prepare the participant's study intervention accordingly. Unblinding will only occur once the entire study is completed, and the database has been locked. The trials active intervention and comparator will be provided by the manufactures and will be identical in shape, colour, and weight.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blinded randomized control trial

Study Record Dates

• First Submitted: September 11, 2024
• First Posted: September 27, 2024
• Study Start: May 27, 2025
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: December 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)