{
  "abstract": "Introduction The treatment of comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) is significantly more challenging than the treatment of either disorder alone. While gold standard evidence-based treatments exist for this comorbidity, clinically significant improvements are only observed in approximately half of clinical trial participants. The use of adjunctive pharmacotherapies, such as 3,4-methylenedioxymethamphetamine (MDMA), may serve to optimise gold standard interventions. The primary aim of the MDMA-assisted PTSD and Alcohol Therapy Trial study is to examine the therapeutic and cost-effectiveness of combining MDMA with evidence-based integrated care for comorbid PTSD+AUD. Specifically, we will examine MDMA-assisted integrated exposure therapy versus active control-assisted integrated exposure therapy in improving treatment outcomes for PTSD+AUD.Methods and analysis This world-first double-blind trial will aim to randomise 100 participants with PTSD+AUD to a regimen of Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) (12 sessions)+MDMA (80–160 mg: 2 dosing and 2 integration sessions) or COPE (12 sessions)+active control (niacin 250 mg: 2 dosing sessions and 2 integration sessions). All participants will receive medical management. The primary PTSD outcome will be the clinician-administered PTSD Scale for DSM-5. The primary drinking outcome will be the number of heavy drinking days (HDDs) per week, validated by phosphatidylethanol. Secondary PTSD and alcohol-related outcomes will include PTSD checklist for DSM-5 scores, absence of any HDDs and standard drinks per drinking day. We will also examine change in other clinical conditions and symptoms including depression, sleep disturbances and post-traumatic cognitions; treatment satisfaction and engagement; adverse events; and cost-effectiveness.Ethics and dissemination This study will be conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and the International Conference on Harmonisation-Good Clinical Practice guidelines. Ethical approval has been granted by the Sydney Local Health District Ethics Review Committee (X22-0121 & 2022/ETH00773). The results of this study will provide world-first data regarding safety, efficacy and cost-effectiveness of MDMA to optimise integrated exposure-based therapy for comorbid AUD and PTSD and will be disseminated to ensure wide accessibility and to support further research and clinical application.Trial registration number NCT05709353.",
  "authors": [
    {
      "affiliations": [
        "Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia",
        "Edith Collins Centre for Translational Research, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales, Australia"
      ],
      "name": "Kirsten C Morley"
    },
    {
      "affiliations": [
        "Eastern Health, Turning Point, Melbourne, Victoria, Australia",
        "Monash Addiction Research Centre, Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia"
      ],
      "name": "S Arunogiri"
    },
    {
      "affiliations": [
        "The Matilda Centre for Research in Mental Health and Substance Use, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "K Mills"
    },
    {
      "affiliations": [
        "Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia",
        "Edith Collins Centre for Translational Research, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales, Australia"
      ],
      "name": "J Watt"
    },
    {
      "affiliations": [
        "The Matilda Centre for Research in Mental Health and Substance Use, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "M Teesson"
    },
    {
      "affiliations": [
        "School of Health Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "A Baillie"
    },
    {
      "affiliations": [
        "Health Economics Group, School of Public Health and Preventative Medicine, Monash University, Melbourne, Victoria, Australia",
        "School of Public Health, The University of Queensland, Brisbane, Queensland, Australia",
        "Queensland Centre for Mental Health Research, Brisbane, Queensland, Australia"
      ],
      "name": "Y Y Lee"
    },
    {
      "affiliations": [
        "National Centre for Mental Health Research, Australian National University, Canberra, Australian Capital Territory, Australia"
      ],
      "name": "A Morse"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA"
      ],
      "name": "S E Back"
    },
    {
      "affiliations": [
        "Eastern Health, Turning Point, Melbourne, Victoria, Australia",
        "Monash Addiction Research Centre, Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia"
      ],
      "name": "D I Lubman"
    },
    {
      "affiliations": [
        "Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia",
        "Edith Collins Centre for Translational Research, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales, Australia"
      ],
      "name": "P S Haber"
    }
  ],
  "title": "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",
  "uid": "33837c61-fbe1-5fc0-86da-467faf4bd96b"
}