PTSDPhase 2MPATHYNCT05709353
MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
A Phase 2 study testing Prolonged exposure therapy, MDMA and Niacin in people with PTSD and Alcohol Use Disorder, run by University of Sydney at 2 sites in Australia.
Trial summary
To explore the effectiveness of of MDMA-assisted prolonged exposure therapy in improving treatment outcomes for individuals with comorbid PTSD and alcohol use disorder in a double-blind randomised placebo-controlled trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PTSD, Alcohol Use Disorder, Alcohol Dependence
- What is being tested?
- Prolonged exposure therapy, MDMA and Niacin
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 2 sitesAustralia
- Study dates
- 19 Sep 2023to May 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Both AUD and current PTSD according to the DSM-5 criteria, for 6 months or longer with at least moderate severity, according to investigator judgement and CAPS-5
- Aged ≥18 years old
- Adequate cognition and English language skills to give valid consent and complete research interviews assessments
- Willing to give written informed consent
- Received prior treatment for PTSD or AUD (not including study interventions)
- Stable housing
- Able to identify a significant other (such as a family/friend/partner) who could accompany them from clinic/provide transport and/or be contacted by the study team if required
Who cannot join
- History of, or currently meeting, DSM-5 criteria for:
- current or lifetime psychotic or bipolar disorders, or
- major depression with psychotic features Assessed via Structured Clinical Interview for DSM-5 - Research Version (SCID-5-RV). Potential participants will be screened for personality disorders but suitability will then be confirmed by clinical interview given the prevalence of high scores in this comorbid population
- Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing)
- Significant alcohol withdrawal (current Clinical Institute Withdrawal Assessment for Alcohol [CIWA-Ar] score ≥10, including history of delirium tremens or alcohol withdrawal seizures).
- Concurrent use of psychotropic medication (antidepressants and alcohol pharmacotherapy use considered if assessed by physician and titrated down with 5 half-lives + 1 week washout)
Show all 14Show fewer
- Use of, and unable or unwilling to cease, any medications likely to interact with MDMA in the opinion of the physicians and investigators during the trial (low dose opiates are permitted for pain management but not the night before or after MDMA sessions)
- Substance use disorder other than tobacco (e.g. benzodiazepines, cannabis)
- Abnormal clinical findings including a history of, or current: cardiac disease and/or dysrhythmia, uncontrolled hypertension or severe hypotension, abnormal electrocardiogram findings, stroke, liver disease, a history of epilepsy, hyponatraemia, or malignant hyperthermia (controlled hypertension and diabetes type II may be permitted)
- Suicide risk according to clinician judgement and responses to Columbia Suicide Severity Rating Scale-Lifetime (C-SSRS-L) and SCID-5-RV.
- Details surrounding any previous attempts >6 months ago will be gathered whereby attempts related to their trauma/PTSD and/or associated with the use of psychostimulants will contribute to risk assessment and guide trial safety measures if enrolled
- Clinically unstable systemic medical (e.g., cancer) or psychiatric disorder or condition that might require hospitalisation that precludes trial participation
- Regular use of ecstasy (e.g. at least twice in last 6 months, or >10 times within the last 5 years)
- Enrolled in any other interventional clinical trials in the previous two months or over the duration of the study
Trial locations and contacts
2 sites in 1 country.
Ellen Towers contact
Australia2 sites, 2 recruiting
- Not yet recruiting
Turning Point
Richmond, Victoria, 3121
Shalini Arunogiri, MBBS, shaliniA@turningpoint.org.au
- Recruiting
Drug Health Services, Royal Prince Alfred Hospital
Sydney, New South Wales, 2050
Paul Haber, MBBS, paul.haber@sydney.edu.au
About this study
Official title: A Randomised, Controlled Trial of MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
To explore the effectiveness of of MDMA-assisted prolonged exposure therapy in improving treatment outcomes for individuals with comorbid PTSD and alcohol use disorder in a double-blind randomised placebo-controlled trial.
Read the detailed description
New strategies for the treatment of comorbid PTSD and alcohol dependence are urgently required. Recent evidence has shown strong support for trauma-focused integrated treatments (namely COPE), however, only 49% demonstrate clinically significant improvements. MDMA may be a promising approach to improve response to COPE for this population. Emerging evidence suggests that MDMA-assisted therapy may be of promise for PTSD, and has demonstrated a good safety profile and potential efficacy in alcohol dependence.
This project will evaluate the clinical efficacy and tolerability of MDMA-assisted COPE relative to a control-assisted COPE. Active control used in this study is niacin. The investigators hypothesise that MDMA treated participants will be have a reduction in PTSD symptom severity as well as heavy drinking.
The trial will utilise a double blind, randomised, controlled design. A sample of 120 individuals will receive 14 weeks of treatment including 12 COPE sessions and 2 dosing sessions with MDMA (80-160mg) or control (niacin 250mg).
- Conditions
- PTSD, Alcohol Use Disorder, Alcohol Dependence, Post-traumatic Stress Disorder, Comorbidities and Coexisting Conditions
- Being tested
- Prolonged exposure therapy, MDMA, Niacin
- Keywords
- MDMA-assisted therapy, Randomised-Controlled Trial, Comorbid PTSD and AUD, MDMA, COPE, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure, Psychedelic-Assisted Therapy
- Medical subject headings
- Stress Disorders, Post-Traumatic, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prolonged exposure therapyBehavioural
Also called COPE (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure)
COPE represents an integration of existing evidence-based manualised CBT interventions for PTSD and substance dependence (see manual DOI: 10.1093/med:psych/9780199334513.001.0001). COPE used in the current study will represent an integration of existing evidence-based manualised CBT interventions for PTSD and substance dependence. COPE only begins when the participant in a safe environment and no longer in contact with the traumatic event/exposure.
COPE employs imaginal and in vivo exposures to treat PTSD and consists of 12 individual 90-minute sessions (i.e. 19.5 hours) delivered by a clinical psychologist.
MDMADrug
Also called 3,4-Methyl enedioxy methamphetamine
Administration of 80 to 160 mg MDMA across two 'dosing' sessions. Supplemental doses (additional 40mg during first session, additional 40- 80mg during second session) will be dependent on clinician and participant consensus during preparatory period of 'dosing session'. These supplemental amounts will be dispensed 60 to 90 minutes after initial 80 mg dose.
NiacinDrug
Also called Control, Vitamin B3
Administration of niacin 250mg or niacin-matched placebo during two 'dosing' sessions.
| Study group | Role | What they receive |
|---|---|---|
| COPE + MDMA | Experimental | 4x COPE sessions
Dose 1:
2x MDMA capsules (80mg) + 1x niacin-matched placebo capsule
Optional supplementary dispense:
1x MDMA capsule (40mg)
4x COPE sessions
Dose 2:
2x MDMA capsules (80mg) + 1x niacin-matched placebo capsule
Optional supplementary dispense:
1x OR 2x white MDMA capsule (40 or 80mg)
4x COPE sessions Receives: Behavioral: Prolonged exposure therapy; Drug: MDMA |
| COPE + Niacin (Control) | Other | 4x COPE sessions
Dose 1:
2x MDMA-matched placebo capsules + 1x niacin capsule (250mg)
Optional supplementary dispense:
1x MDMA-matched placebo capsule
4x COPE sessions
Dose 2:
2x MDMA-matched placebo capsules + 1x niacin capsule (250mg)
Optional supplementary dispense:
1x OR 2x MDMA-matched placebo capsule
4x COPE sessions Receives: Behavioral: Prolonged exposure therapy; Drug: Niacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in clinician-rated PTSD severity via Clinician-Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) (CAPS-5) from baseline to visit 16.
CAPS-5 is a structured diagnostic interview with excellent psychometric properties and diagnostic efficiency and used widely in MDMA-assisted PTSD studies. The CAPS-5 will be administered by independent evaluators blind to treatment condition.
CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms.
CAPS-5 symptom cluster severity scores are calculated by summing the individual item severity scores for symptoms corresponding to a given DSM-5 cluster: Criterion B (items 1-5); Criterion C (items 6-7); Criterion D (items 8-14); and, Criterion E (items 15-20).
Measured: 52 weeks
change in self-reported PTSD symptom severity via Post-Traumatic Stress Disorder Checklist for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) (PCL-5) from baseline to visit 16.
PCL-5 has excellent psychometric characteristics for a secondary indicator of PTSD symptom severity.
Items are summed to provide a total severity score (range = 0-80). The PCL-5 can determine a provisional diagnosis in two ways: Summing all 20 items (range 0-80) and using a cut-point score of 31-33 appears to be reasonable based upon current psychometric work.
Measured: 52 weeks
Secondary outcomes (2)
Number of Heavy Drinking Days per week (HDDs) (>5 standard drinks/day for men; >4 for women)
This will be measured by the Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Measured: 52 weeks
Absence of any HDD
Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2023
- Study start19 Sep 2023
- Primary completionMay 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised, double-blind between group comparison of change in PTSD symptoms and alcohol consumption
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sydney
- Sponsor type
- University, hospital or other
- Collaborators
- Monash University, Sydney Local Health District
- Responsible party
- Sponsor
- Investigators
- Kirsten C Morley, PhD, Principal investigator, University of Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05709353
- Sponsor's protocol ID
- X22-0121
- Acronym
- MPATHY
- Status last verified
- Nov 2023
- First submitted
- 20 Jan 2023
- Last updated
- 7 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Morley KC, Arunogiri S, Mills K, Watt J, Teesson M, Baillie A, Lee YY, Morse A, Back SE, Lubman DI, Haber PS. MDMA-assisted PTSD and Alcohol Therapy Trial (MPATHY): study protocol for a double-blind, randomised, controlled outpatient trial of MDMA-assisted integrated exposure-based therapy for comorbid post-traumatic stress disorder and alcohol use disorder. BMJ Open. 2026 Jul 6;16(7):e114896. doi: 10.1136/bmjopen-2025-114896.
PubMed 42409408
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Controlled Trial of MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT05709353
- Acronym / sponsor ID
- MPATHY / X22-0121
- Conditions
- PTSD, Alcohol Use Disorder, Alcohol Dependence, Post-traumatic Stress Disorder, Comorbidities and Coexisting Conditions
- Keywords
- MDMA-assisted therapy, Randomised-Controlled Trial, Comorbid PTSD and AUD, MDMA, COPE, Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure, Psychedelic-Assisted Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of SydneyUniversity, hospital or other
- Collaborators
- Monash University, Sydney Local Health District
- Study start
- 19 Sep 2023 (actual)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 2 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To explore the effectiveness of of MDMA-assisted prolonged exposure therapy in improving treatment outcomes for individuals with comorbid PTSD and alcohol use disorder in a double-blind randomised placebo-controlled trial.
Detailed description
New strategies for the treatment of comorbid PTSD and alcohol dependence are urgently required. Recent evidence has shown strong support for trauma-focused integrated treatments (namely COPE), however, only 49% demonstrate clinically significant improvements. MDMA may be a promising approach to improve response to COPE for this population. Emerging evidence suggests that MDMA-assisted therapy may be of promise for PTSD, and has demonstrated a good safety profile and potential efficacy in alcohol dependence.
This project will evaluate the clinical efficacy and tolerability of MDMA-assisted COPE relative to a control-assisted COPE. Active control used in this study is niacin. The investigators hypothesise that MDMA treated participants will be have a reduction in PTSD symptom severity as well as heavy drinking.
The trial will utilise a double blind, randomised, controlled design. A sample of 120 individuals will receive 14 weeks of treatment including 12 COPE sessions and 2 dosing sessions with MDMA (80-160mg) or control (niacin 250mg).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomised, double-blind between group comparison of change in PTSD symptoms and alcohol consumption
| Arm | Type | Receives |
|---|---|---|
| COPE + MDMA | Experimental | Behavioral: Prolonged exposure therapy, Drug: MDMA4x COPE sessions Dose 1: 2x MDMA capsules (80mg) + 1x niacin-matched placebo capsule Optional supplementary dispense: 1x MDMA capsule (40mg) 4x COPE sessions Dose 2: 2x MDMA capsules (80mg) + 1x niacin-matched placebo capsule Optional supplementary dispense: 1x OR 2x white MDMA capsule (40 or 80mg) 4x COPE sessions |
| COPE + Niacin (Control) | Other | Behavioral: Prolonged exposure therapy, Drug: Niacin4x COPE sessions Dose 1: 2x MDMA-matched placebo capsules + 1x niacin capsule (250mg) Optional supplementary dispense: 1x MDMA-matched placebo capsule 4x COPE sessions Dose 2: 2x MDMA-matched placebo capsules + 1x niacin capsule (250mg) Optional supplementary dispense: 1x OR 2x MDMA-matched placebo capsule 4x COPE sessions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Both AUD and current PTSD according to the DSM-5 criteria, for 6 months or longer with at least moderate severity, according to investigator judgement and CAPS-5
- Aged ≥18 years old
- Adequate cognition and English language skills to give valid consent and complete research interviews assessments
- Willing to give written informed consent
- Received prior treatment for PTSD or AUD (not including study interventions)
Key exclusion criteria (14 listed)
- History of, or currently meeting, DSM-5 criteria for:
- Pregnant or lactating (contraception must be used and a sensitive pregnancy test will be performed at baseline and prior to dosing)
- Significant alcohol withdrawal (current Clinical Institute Withdrawal Assessment for Alcohol [CIWA-Ar] score ≥10, including history of delirium tremens or alcohol withdrawal seizures).
- Concurrent use of psychotropic medication (antidepressants and alcohol pharmacotherapy use considered if assessed by physician and titrated down with 5 half-lives + 1 week washout)
- Use of, and unable or unwilling to cease, any medications likely to interact with MDMA in the opinion of the physicians and investigators during the trial (low dose opiates are permitted for pain management but not the night before or after MDMA sessions)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prolonged exposure therapyAlso: COPE (Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure)COPE represents an integration of existing evidence-based manualised CBT interventions for PTSD and substance dependence (see manual DOI: 10.1093/med:psych/9780199334513.001.0001). COPE used in the current study will represent an integration of existing evidence-based manualised CBT interventions for PTSD and substance dependence. COPE only begins when the participant in a safe environment and no longer in contact with the traumatic event/exposure. COPE employs imaginal and in vivo exposures to treat PTSD and consists of 12 individual 90-minute sessions (i.e. 19.5 hours) delivered by a clinical psychologist. | Behavioural | COPE + MDMA, COPE + Niacin (Control) |
| MDMAAlso: 3,4-Methyl enedioxy methamphetamineAdministration of 80 to 160 mg MDMA across two 'dosing' sessions. Supplemental doses (additional 40mg during first session, additional 40- 80mg during second session) will be dependent on clinician and participant consensus during preparatory period of 'dosing session'. These supplemental amounts will be dispensed 60 to 90 minutes after initial 80 mg dose. | Drug | COPE + MDMA |
| NiacinAlso: Control, Vitamin B3Administration of niacin 250mg or niacin-matched placebo during two 'dosing' sessions. | Drug | COPE + Niacin (Control) |
Primary outcome
change in clinician-rated PTSD severity via Clinician-Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) (CAPS-5) from baseline to visit 16.
Time frame: 52 weeks
CAPS-5 is a structured diagnostic interview with excellent psychometric properties and diagnostic efficiency and used widely in MDMA-assisted PTSD studies. The CAPS-5 will be administered by independent evaluators blind to treatment condition. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 DSM-5 PTSD symptoms. CAPS-5 symptom cluster severity scores are calculated by summing the individual item severity scores for symptoms corresponding to a given DSM-5 cluster: Criterion B (items 1-5); Criterion C (items 6-7); Criterion D (items 8-14); and, Criterion E (items 15-20).
change in self-reported PTSD symptom severity via Post-Traumatic Stress Disorder Checklist for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) (PCL-5) from baseline to visit 16.
Time frame: 52 weeks
PCL-5 has excellent psychometric characteristics for a secondary indicator of PTSD symptom severity. Items are summed to provide a total severity score (range = 0-80). The PCL-5 can determine a provisional diagnosis in two ways: Summing all 20 items (range 0-80) and using a cut-point score of 31-33 appears to be reasonable based upon current psychometric work.
2 secondary outcomes
Number of Heavy Drinking Days per week (HDDs) (>5 standard drinks/day for men; >4 for women)
Time frame: 52 weeks
Absence of any HDD
Time frame: 52 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2023.
- Derived from this study: PubMed 42409408Morley KC, Arunogiri S, Mills K, Watt J, Teesson M, Baillie A, Lee YY, Morse A, Back SE, Lubman DI, Haber PS. MDMA-assisted PTSD and Alcohol Therapy Trial (MPATHY): study protocol for a double-blind, randomised, controlled outpatient trial of MDMA-assisted integrated exposure-based therapy for comorbid post-traumatic stress disorder and alcohol use disorder. BMJ Open. 2026 Jul 6;16(7):e114896. doi: 10.1136/bmjopen-2025-114896.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ellen Towers contact
Kirsten C Morley, PhD principal investigator
University of Sydney
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prolonged exposure therapy, MDMA and Niacin in people with PTSD and Alcohol Use Disorder, run by University of Sydney at 2 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kirsten C Morley, PhD (61295153636, Kirsten.morley@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in clinician-rated PTSD severity via Clinician-Administered PTSD Scale for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) (CAPS-5) from baseline to visit 16. (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05709353, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.