Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001100381
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
12/08/2026
Date registered
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4/09/2026
Date last updated
Help: Date last updated
4/09/2026
Date data sharing statement initially provided
Help: Data sharing statement date
4/09/2026
Type of registration
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Prospectively registered

Titles & IDs
Public title
Psilocybin-assisted treatment for methamphetamine use disorder: A multi-site randomised controlled trial (PsiMA RCT)
Scientific title
Psilocybin-assisted treatment for methamphetamine use disorder: A multi-site randomised controlled trial (PsiMA RCT)
Additional trial identifiers [1] 318166 0
Nil
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Methamphetamine Use Disorder 343219 0
Condition category
Condition code
Mental Health 339306 339306 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Intervention: Psilocybin-assisted psychotherapy (PAT-25)

International Non-proprietary Name (INN): Psilocybin

Dose: Single 25 mg oral dose of psilocybin.

Duration of treatment: Approximately five weeks. Participants receive three 90-minute preparatory psychotherapy sessions during the two weeks preceding psilocybin administration, followed by a single supervised 6–8-hour psilocybin dosing session. Three 90-minute integration psychotherapy sessions are then provided after dosing: the first occurs in the same week as the dosing session, and the second and third occur at approximately weekly intervals over the subsequent two weeks.

Psychotherapy and mode of delivery: Psychotherapy is delivered by trained study therapists who are clinical psychologists, psychotherapists or psychiatrists, using a lead therapist and co-therapist model. The lead therapist delivers the three preparatory psychotherapy sessions and the three post-dose integration psychotherapy sessions, providing continuity of therapeutic care across the intervention. The co-therapist joins the lead therapist for one of the preparation sessions, the psilocybin dosing session and one of the integration sessions.

The three preparatory sessions occur before psilocybin administration and focus on establishing the therapeutic relationship, preparing the participant for the dosing experience, discussing expectations and concerns, and developing strategies for managing potentially challenging experiences.

Participants then receive a single 25 mg oral dose of psilocybin during a supervised 6–8-hour dosing session in a controlled clinical setting. Both the lead therapist and co-therapist are present throughout the dosing session to provide psychological support and monitoring.

Following psilocybin administration, the lead therapist conducts three 90-minute integration psychotherapy sessions. The first occurs in the same week as the dosing session, with the second and third occurring at approximately weekly intervals over the subsequent two weeks. Integration sessions support participants to reflect on and make meaning of their dosing experience and consider how experiences or insights arising from the session may relate to their treatment goals, including methamphetamine use and recovery.

Adherence: Psilocybin is administered directly by authorised study personnel at the study site, with administration documented in investigational product accountability records. Attendance at psychotherapy sessions is monitored and recorded. As the investigational product is administered as a single supervised dose, participant self-administration and medication adherence monitoring are not required.

Optional open-label treatment: Participants will be followed for 52 weeks. Following completion of the Week 16 assessment, participants may elect to receive an optional open-label 25 mg psilocybin-assisted psychotherapy treatment. Receipt of the open-label treatment is conditional on the participant choosing to proceed and remaining clinically suitable for further psilocybin-assisted treatment. Participants will not proceed where there have been significant safety concerns, including a serious adverse event (SAE) that raises concern regarding further treatment, or where the participant's therapy dyad identifies clinical or safety concerns regarding further treatment.

The optional open-label treatment occurs after completion of the randomised comparison period. Outcomes following the open-label treatment will be analysed separately from the primary randomised comparison and will not be combined with the blinded treatment period when estimating the effect of the randomised PAT-25 versus comparator intervention.
Intervention code [1] 335052 0
Treatment: Drugs
Intervention code [2] 335053 0
Treatment: Other
Description of the comparator or control
INN: Psilocybin

Dose: Single 5 mg dose

Duration of treatment: Approximately five weeks. Participants receive three 90-minute preparatory psychotherapy sessions during the two weeks preceding psilocybin administration, followed by a single supervised 6–8-hour psilocybin dosing session. Three 90-minute integration psychotherapy sessions are then provided after dosing: the first occurs in the same week as the dosing session, and the second and third occur at approximately weekly intervals over the subsequent two weeks.

Psychotherapy and mode of delivery: Psychotherapy is delivered by trained study therapists who are clinical psychologists, psychotherapists or psychiatrists, using a lead therapist and co-therapist model. The lead therapist delivers the three preparatory psychotherapy sessions and the three post-dose integration psychotherapy sessions, providing continuity of therapeutic care across the intervention. The co-therapist joins the lead therapist for one of the preparation sessions, the psilocybin dosing session and one of the integration sessions.

The three preparatory sessions occur before psilocybin administration and focus on establishing the therapeutic relationship, preparing the participant for the dosing experience, discussing expectations and concerns, and developing strategies for managing potentially challenging experiences.

Participants then receive a single 5 mg oral dose of psilocybin during a supervised 6–8-hour dosing session in a controlled clinical setting. Both the lead therapist and co-therapist are present throughout the dosing session to provide psychological support and monitoring.

Following psilocybin administration, the lead therapist conducts three 90-minute integration psychotherapy sessions. The first occurs in the same week as the dosing session, with the second and third occurring at approximately weekly intervals over the subsequent two weeks. Integration sessions support participants to reflect on and make meaning of their dosing experience and consider how experiences or insights arising from the session may relate to their treatment goals, including methamphetamine use and recovery.

Adherence: Psilocybin is administered directly by authorised study personnel at the study site, with administration documented in investigational product accountability records. Attendance at psychotherapy sessions is monitored and recorded. As the investigational product is administered as a single supervised dose, participant self-administration and medication adherence monitoring are not required.

Optional open-label treatment: Participants will be followed for 52 weeks. Following completion of the Week 16 assessment, participants may elect to receive an optional open-label 25 mg psilocybin-assisted psychotherapy treatment. Receipt of the open-label treatment is conditional on the participant choosing to proceed and remaining clinically suitable for further psilocybin-assisted treatment. Participants will not proceed where there have been significant safety concerns, including a serious adverse event (SAE) that raises concern regarding further treatment, or where the participant's therapy dyad identifies clinical or safety concerns regarding further treatment.

The optional open-label treatment occurs after completion of the randomised comparison period. Outcomes following the open-label treatment will be analysed separately from the primary randomised comparison and will not be combined with the blinded treatment period when estimating the effect of the randomised PAT-25 versus comparator intervention.
Control group
Dose comparison

Outcomes
Primary outcome [1] 346529 0
Number of days of self-reported methamphetamine use during the 28 days preceding the week 12 assessment supported by urine drug analysis.
Timepoint [1] 346529 0
12 weeks post-randomisation (covering drug use in the 28 days prior to this time point) Weekly urine drug screening and TLFB measurements.
Secondary outcome [1] 466249 0
Continuous abstinence from methamphetamine following completion of the treatment intervention.
Timepoint [1] 466249 0
Continuous abstinence assessed from week 5 to weeks 8, 12 and 16 post-randomisation.
Secondary outcome [2] 466250 0
Between group difference in proportion of urine drug tests negative for methamphetamine.
Timepoint [2] 466250 0
Between week 5 and weeks 8, 12 and 16 post-randomisation
Secondary outcome [3] 466251 0
Proportion of participants demonstrating a clinically meaningful reduction in methamphetamine use compared with baseline.
Timepoint [3] 466251 0
Weeks 8, 12, 16, 20, 28, 36 and 52 post-randomisation.
Secondary outcome [4] 466252 0
Proportion of participants meeting criteria for clinical remission from methamphetamine use disorder (MAUD), defined as no methamphetamine use during the preceding 28 days AND fewer than two DSM-5 MAUD criteria during the preceding 28 days.
Timepoint [4] 466252 0
Week 16 post-randomisation.
Secondary outcome [5] 466253 0
Total number of days of methamphetamine use following completion of the treatment intervention.
Timepoint [5] 466253 0
Cumulative methamphetamine use assessed over the periods from week 5 to weeks 8, 12 and 16 post-randomisation.
Secondary outcome [6] 466254 0
Number of days of use of any other substance other than methamphetamine, alcohol and nicotine, during the preceding 28 days.
Timepoint [6] 466254 0
Weeks 8, 12, 16, 20, 28, 36 and 52 post-randomisation.
Secondary outcome [7] 466255 0
Symptoms of depression, anxiety and psychological distress as composite measure.
Timepoint [7] 466255 0
Weeks 8, 12 and 16 post-randomisation.
Secondary outcome [8] 466256 0
Severity of methamphetamine craving.
Timepoint [8] 466256 0
Weeks 8, 12 and 16 post-randomisation for the specified between-group secondary endpoint. The protocol collects the VAS more frequently during the study, but these are the explicitly nominated secondary endpoint timepoints.
Secondary outcome [9] 466257 0
Severity of adverse consequences/problems associated with substance use.
Timepoint [9] 466257 0
Weeks 8, 12 and 16 post-randomisation.
Secondary outcome [10] 466258 0
Severity of insomnia symptoms.
Timepoint [10] 466258 0
Weeks 5, 12, 16 and 52 post randomisation
Secondary outcome [11] 466259 0
Health-related quality of life.
Timepoint [11] 466259 0
Weeks 5, 12, 16, 24, 52 post randomisation.
Secondary outcome [12] 466260 0
Functional impairment associated with health and substance use.
Timepoint [12] 466260 0
Weeks 5, 12, 24, 52 post randomisation
Secondary outcome [13] 466261 0
Safety and tolerability of psilocybin-assisted psychotherapy, including the incidence, severity and seriousness of adverse events and adverse reactions.
Timepoint [13] 466261 0
Continuously from study enrolment through study follow-up, with safety assessed at scheduled study visits. Study visits are weekly from weeks 0 to 16 then at weeks 20, 28, 32 and 52.
Secondary outcome [14] 466263 0
Cost-effectiveness of PAT-25 compared with PAT-5 as composite end point
Timepoint [14] 466263 0
Resource-use and quality-of-life data collected longitudinally during study follow-up, with economic evaluation incorporating outcomes through 52 weeks.
Secondary outcome [15] 466786 0
Number of days of use of alcohol during the preceding 28 days.
Timepoint [15] 466786 0
Weeks 8, 12, 16, 20, 28, 36 and 52 post-randomisation.
Secondary outcome [16] 466787 0
Number of days of use of nicotine during the preceding 28 days.
Timepoint [16] 466787 0
Weeks 8, 12, 16, 20, 28, 36 and 52 post-randomisation.
Secondary outcome [17] 466788 0
Quality of Life
Timepoint [17] 466788 0
Weeks 5, 12, 16, 24, 52 post randomisation.
Secondary outcome [18] 466855 0
Affective attitude toward the intervention
Timepoint [18] 466855 0
Week 16 post randomisation
Secondary outcome [19] 466856 0
Burden of the intervention
Timepoint [19] 466856 0
Week 16 post randomisation
Secondary outcome [20] 466857 0
Ethicality of the intervention
Timepoint [20] 466857 0
Week 16 post randomisation
Secondary outcome [21] 466858 0
Intervention coherence
Timepoint [21] 466858 0
Week 16 post randomisation
Secondary outcome [22] 466859 0
Opportunity costs
Timepoint [22] 466859 0
Week 16 post randomisation
Secondary outcome [23] 466860 0
Perceived effectiveness
Timepoint [23] 466860 0
Week 16 post randomisation
Secondary outcome [24] 466861 0
Self-efficacy
Timepoint [24] 466861 0
Week 16 post randomisation
Secondary outcome [25] 466862 0
Overall acceptability
Timepoint [25] 466862 0
Week 16 post randomisation

Eligibility
Key inclusion criteria
Aged 25 years or older.
Meets DSM-5 criteria for methamphetamine use disorder (MAUD).
Methamphetamine use on 6–28 days during the 28 days prior to screening.
Independent verification of recent methamphetamine use within 28 days of trial registration (e.g. positive urine drug screen or written confirmation from an external therapist/treatment facility).
Currently seeking treatment for MAUD and engaged with a therapist external to the study, with intention to continue treatment/support following completion of week 12.
In good general health, as determined by medical history and physical examination.
Able to abstain from illicit or extra-medical drug and alcohol use for at least 2 days prior to psilocybin dosing.
Able to engage with psychotherapy and establish adequate therapeutic alliance with the study therapy team prior to dosing.
Has an available friend or family member and suitable home-like environment to provide support for the 24 hours following psilocybin dosing.
Able to complete study follow-up, read and write in English, and swallow capsules.
Minimum age
25 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
Pregnant or breastfeeding, or of childbearing potential and unwilling to avoid pregnancy during the study.
History of bipolar I or II disorder.
History of anorexia nervosa or bulimia nervosa.
First- or second-degree relative with a history of a psychotic disorder or bipolar I or II disorder.
Suicidal or homicidal behaviours within the previous 6 months, as assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS).
History of drug-induced psychosis resulting in presentation to an emergency department or acute mental health facility, or hospital admission.
Severe psychiatric illness other than substance use disorder requiring acute hospitalisation within the previous 4 years, or another psychiatric condition considered to compromise participant safety.
Current dexamphetamine or lisdexamfetamine treatment.
Uncontrolled hypertension, defined as >140/90 mmHg despite treatment with a single antihypertensive.
Medically significant illness considered by the study medical officer to make participation unsuitable, including unstable diabetes, epilepsy, severe cardiovascular disease, significant hepatic disease or renal failure requiring dialysis.
Current use of contraindicated medications, including monoamine oxidase inhibitors, antipsychotics, St John’s Wort, or other medications considered unsuitable by the study medical officer.
Illicit drug use, extra-medical benzodiazepine or opioid use within 2 days before psilocybin administration. Participants receiving opioid substitution therapy may be included if otherwise eligible.
Use of a classical hallucinogen (including LSD, DMT, psilocybin, mescaline, salvia divinorum or ibogaine) within 28 days before screening.
Unstable housing or homelessness.
Anticipated inability to complete follow-up, for example planned relocation, extended travel or likely imprisonment.

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)
Participants will be randomised in a 1:1 ratio using an electronically generated allocation schedule prepared by an independent statistician. Randomisation will be stratified by study site using variable block sizes. The allocation schedule will be provided only to the unblinded trial pharmacists at each site. Investigators, study staff, therapists and participants will not have access to the allocation sequence. Study medication will be dispensed as indistinguishable capsules according to the randomisation schedule, thereby maintaining allocation concealment until treatment assignment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
permuted block randomisation
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
The target sample size is 120 participants, randomised 1:1 between treatment groups. The sample size calculation was based on the primary outcome of number of days of methamphetamine use in the preceding 28 days. Pilot study data indicated a mean of 12.5 days of methamphetamine use over 28 days at baseline. Assuming a 30% reduction in the comparator group to a mean of 8.7 days, trial data were simulated using a negative binomial distribution with a size parameter of 2.5. A sample of 80 participants with primary endpoint data (40 per group) provides 90% power to detect a between-group difference of 4 days of methamphetamine use, using a two-sided significance level of 5%. Allowing for up to 30% attrition, 120 participants will be enrolled.

The primary analysis will follow the intention-to-treat principle. The primary outcome, number of days of methamphetamine use in the 28 days prior to the week 12 assessment, will be modelled using negative binomial regression. Treatment allocation will be included as an indicator variable and the treatment effect will be estimated with its associated 95% confidence interval.

Secondary outcomes with repeated measurements will be analysed using generalised linear mixed models, with treatment group and the baseline value of the relevant outcome included as fixed effects and a participant-level random effect included to account for repeated measurements within participants. The distribution and link function will be selected as appropriate to the outcome type. Analyses will use the intention-to-treat population. Where outcome data are missing, multiple imputation will be used to support the intention-to-treat analysis. If a treatment effect is demonstrated, exploratory mediation analyses will be undertaken to investigate potential treatment-effect mediators.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/11/2026
Actual
Date of last participant enrolment
Anticipated
3/12/2029
Actual
Date of last data collection
Anticipated
29/11/2030
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 29985 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 29986 0
Drug and Alcohol Clinical Services, Hunter New England Local Health District - Newcastle
Recruitment hospital [3] 29987 0
Turning Point Drug and Alcohol Centre - Richmond
Recruitment postcode(s) [1] 46377 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 46378 0
2300 - Newcastle
Recruitment postcode(s) [3] 46379 0
3121 - Richmond

Funding & Sponsors
Funding source category [1] 322729 0
Government body
Name [1] 322729 0
Australian Department of Health, Disability and Ageing, Medical Research Future Fund (MRFF)
Country [1] 322729 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
Country
Australia
Secondary sponsor category [1] 325651 0
None
Name [1] 325651 0
Address [1] 325651 0
Country [1] 325651 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 321172 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 321172 0
Ethics committee country [1] 321172 0
Australia
Date submitted for ethics approval [1] 321172 0
25/05/2026
Approval date [1] 321172 0
24/07/2026
Ethics approval number [1] 321172 0
2026_ETH01194

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

Contacts
Principal investigator
Name 152902 0
Prof Jonathan Brett
Address 152902 0
Clinical Therapeutics, Level 2 Xavier Building, St. Vincent's Hospital, 390 Victoria Street, Darlinghurst, Sydney, 2010, New South Wales
Country 152902 0
Australia
Phone 152902 0
+61283821111
Fax 152902 0
Email 152902 0
[email protected]
Contact person for public queries
Name 152903 0
Rochelle Thornton
Address 152903 0
Hunter Medical Research Institute, Lot 1 Kookaburra Cct, New Lambton Heights NSW 2305
Country 152903 0
Australia
Phone 152903 0
+61 2 404 20886
Fax 152903 0
Email 152903 0
[email protected]
Contact person for scientific queries
Name 152904 0
Jonathan Brett
Address 152904 0
Clinical Therapeutics, Level 2 Xavier Building, St. Vincent's Hospital, 390 Victoria Street, Darlinghurst, Sydney, 2010, New South Wales
Country 152904 0
Australia
Phone 152904 0
+61283821111
Fax 152904 0
Email 152904 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.