Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626000576325
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
18/02/2026
Date registered
Help: Date registered
7/05/2026
Date last updated
Help: Date last updated
7/05/2026
Date data sharing statement initially provided
Help: Data sharing statement date
7/05/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
Psilocybin-Assisted Concussion Therapy for Persisting Post-Concussion Symptoms
Scientific title
Psilocybin-assisted concussion therapy for persistent post-concussion symptoms: a double-blind randomised active-placebo controlled trial in participants with mild traumatic brain injury
Additional trial identifiers [1] 316379 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PACT-201
Related trial records

Health condition
Health condition(s) studied:
Persistent post-concussion symptoms 340469 0
Mild traumatic brain injury 341059 0
Condition category
Condition code
Neurological 336674 336674 0 0
Other neurological disorders
Injuries and Accidents 337185 337185 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
A double-blind randomised controlled trial testing the addition of a single 25mg dose of psilocybin administered via oral capsule at week 4.

Psychotherapeutic intervention will involve in-person, 2hour-long sessions with a co-therapy team of psilocybin therapists. Three weekly Preparation sessions will be held for three weeks prior to dosing, and four Integration psychotherapy sessions will occur during a six-week period starting the day after the Dosing session. In addition to the in-person integration, a High-Intensity Self-Directed Integration program will be completed daily by participants in their own time for approximately 30 minutes to 1 hour for 2 weeks post-dose. The High-Intensity Self-Directed Integration program will involve core topics such as understanding symptoms and recovery, restoring sleep, emotion and stress management, physical reconnection, and exploring meaning and motivation. Adherence in psychotherapy will be assessed by attendance and via review of self-directed integration documents.
Intervention code [1] 333043 0
Treatment: Drugs
Intervention code [2] 333044 0
Treatment: Other
Description of the comparator or control
A single 5 mg dose of psilocybin administered via oral capsule at week 4, alongside 10 weeks of psychotherapeutic intervention and self-directed therapy consistent with the intervention group.
Control group
Dose comparison

Outcomes
Primary outcome [1] 344189 0
Persistent post-concussion symptoms
Timepoint [1] 344189 0
Baseline, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 (Primary endpoint), 14, 18, 22, 26 weeks after baseline
Secondary outcome [1] 456973 0
Quality of life
Timepoint [1] 456973 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [2] 456974 0
Quality of life
Timepoint [2] 456974 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [3] 456975 0
Disability
Timepoint [3] 456975 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [4] 456976 0
Functioning and productivity
Timepoint [4] 456976 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [5] 456977 0
Depression
Timepoint [5] 456977 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [6] 456978 0
Depression
Timepoint [6] 456978 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [7] 456979 0
Anxiety
Timepoint [7] 456979 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [8] 456980 0
Post-traumatic stress disorder
Timepoint [8] 456980 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [9] 456981 0
Substance use
Timepoint [9] 456981 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [10] 456982 0
Headache
Timepoint [10] 456982 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [11] 456983 0
Sleep
Timepoint [11] 456983 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [12] 456985 0
Psychological inflexibility and experiential avoidance
Timepoint [12] 456985 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [13] 456987 0
Emotion dysregulation
Timepoint [13] 456987 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [14] 456989 0
Experiential avoidance
Timepoint [14] 456989 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [15] 456990 0
Life satisfaction
Timepoint [15] 456990 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [16] 456991 0
Productivity
Timepoint [16] 456991 0
Baseline, 26 weeks post commencement
Secondary outcome [17] 456992 0
Healthcare Utilisation
Timepoint [17] 456992 0
Baseline, 26 weeks post commencement
Secondary outcome [18] 456994 0
Visual-spatial reasoning, planning, and visual memory
Timepoint [18] 456994 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [19] 456995 0
Executive functioning and inhibitory control
Timepoint [19] 456995 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [20] 456996 0
Cognitive flexibility
Timepoint [20] 456996 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [21] 456997 0
New learning memory and delayed recall
Timepoint [21] 456997 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [22] 456998 0
Attention and working memory
Timepoint [22] 456998 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [23] 456999 0
Processing, attentional shifting, executive functioning, and cognitive flexibility
Timepoint [23] 456999 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [24] 457000 0
Verbal fluency
Timepoint [24] 457000 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [25] 457001 0
Cognitive fusion
Timepoint [25] 457001 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [26] 457002 0
Blood biomakers
Timepoint [26] 457002 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [27] 457003 0
Neuroimaging
Timepoint [27] 457003 0
Baseline, 10 weeks post-baseline
Secondary outcome [28] 457923 0
Somatisation
Timepoint [28] 457923 0
Baseline, 5, 10, 26 weeks post-baseline
Secondary outcome [29] 458926 0
Neuroimaging
Timepoint [29] 458926 0
Baseline, 10 weeks post-baseline
Secondary outcome [30] 458929 0
Neuroimaging
Timepoint [30] 458929 0
Baseline, 10 weeks post-baseline
Secondary outcome [31] 458930 0
Quality of Life
Timepoint [31] 458930 0
Baseline, 5, 10, 26 weeks post-baseline

Eligibility
Key inclusion criteria
--Be aged 18 to 65 years.
--Be able to swallow capsules.
--Have a diagnosis of previous mild traumatic brain injury: less than 30 min of loss of consciousness; and less than 24 h of post-traumatic amnesia (PTA).
--Have a stable clinician diagnosis of persistent post-concussion symptoms (PPCS) for a minimum of 6 months.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
--Have a current or lifetime history of meeting DSM-5 criteria for Schizophrenia, other Psychotic Disorder, Dissociative Identity Disorder, or Bipolar I or II Disorder or other mood disorder with psychotic features.
--Have a current or past year history of meeting DSM-5 criteria for alcohol or drug dependence (excluding caffeine and nicotine), if determined by the PI or Study Physician to be incompatible with safe exposure to psilocybin.
--Have current serious suicide risk, as determined through psychiatric interview, responses to ColumbiaSuicide Severity Rating Scale (C-SSRS), and clinical judgment of the AP or treating team
--Require ongoing concomitant therapy with an excluded medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by an independent randomisation monitor (research staff not otherwise involved in the trial)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software, stratified by age, sex assigned at birth, and duration of illness.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
A full Statistical Analysis Plan will be pre-registered before completion of the trial and data lock.

Primary analysis:
Conducted after all participants reach Study Termination and the study database has been locked. All outcome analyses will be based on the mITT analysis set. The primary outcome measure of effectiveness will be the difference in mean RPQ scores between groups (25 mg therapeutic dosage vs 4 mg active-placebo dosage) at the PE – week 10 (6 weeks post-psilocybin). 95% CIs will be calculated for the estimated mean group difference in RPQ scores. Missing data will not be imputed and will be assumed missing at random (MAR). Sensitivityanalyses will be conducted to assess the potential impact of departures from the MAR assumption.

Secondary analysis:
Binary endpoints will use log-binomial regression or exact logistic regression to approximatethese values if the numbers in either arm are fewer than 5. Change scores will be analysed usingappropriate regression models. Where an outcome has two or more measures of change scores, repeatedmeasures analysis will be undertaken. For skewed data, estimated differences between medians and their 95% CIs will be computed via quantile regression.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2026
Actual
Date of last participant enrolment
Anticipated
1/07/2029
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 320990 0
Government body
Name [1] 320990 0
Department of Health, Disability and Ageing Medical Research Future Fund: 2024 MRFF Traumatic Brain Injury S2-4
Country [1] 320990 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Country
Australia
Secondary sponsor category [1] 323688 0
None
Name [1] 323688 0
Address [1] 323688 0
Country [1] 323688 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 319523 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 319523 0
Ethics committee country [1] 319523 0
Australia
Date submitted for ethics approval [1] 319523 0
12/11/2025
Approval date [1] 319523 0
09/01/2026
Ethics approval number [1] 319523 0
48912

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 147598 0
Dr Paul Liknaitzky
Address 147598 0
Clinical Psychedelic Lab, Monash University, Level 1, Building 2 270 Ferntree Gully Rd Notting Hill, VIC 3168
Country 147598 0
Australia
Phone 147598 0
+61 3 990 30855
Fax 147598 0
Email 147598 0
[email protected]
Contact person for public queries
Name 147599 0
Josh Allen
Address 147599 0
Clinical Psychedelic Lab, Monash University, Level 1, Building 2 270 Ferntree Gully Rd Notting Hill, VIC 3168
Country 147599 0
Australia
Phone 147599 0
+61 3 99050100
Fax 147599 0
Email 147599 0
[email protected]
Contact person for scientific queries
Name 147600 0
Paul Liknaitzky
Address 147600 0
Clinical Psychedelic Lab, Monash University, Level 1, Building 2 270 Ferntree Gully Rd Notting Hill, VIC 3168
Country 147600 0
Australia
Phone 147600 0
+61 3 99050100
Fax 147600 0
Email 147600 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.