MDMA-Assisted Psychotherapy for the Treatment of PTSD
Research type
Research Study
Full title
An Open- Label, Phase 2, Multicenter Feasibility Study if Manualized MDMA-Assisted Psychotherapy with an fMRI sub-study Assessing Changes in Brain Activity in Subjects with Posttraumatic Stress Disorder.
IRAS ID
260801
Contact name
Fabiana da Silva Alves
Contact email
Sponsor organisation
MAPS Europe B.V.
Eudract number
2018-001718-13
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 8 months, 0 days
Research summary
Research Summary
Post-traumatic stress disorder (PTSD) is a serious disorder that negatively impacts a person’s daily life, causes expensive healthcare use and increases risk of depression and suicide. Treatment of PTSD using psychotherapy and/or antidepressants is either not effective or intolerable in up to half of patients. 3,4-methylendioxymethamphetamine (MDMA) is a monoamine releaser and re-uptake inhibitor with effects on neurohormone release; it affects certain brain chemicals by causing more of them to be released and making their effects last longer. These combined biological effects reduce mental defenses and fear of emotional harm, improves communication and can increase empathy. This in return creates a mental state very useful in psychotherapy.
This will be the first multi-site study of MDMA-assisted psychotherapy (talk therapy) for PTSD in Europe and is the lead-in to a Phase 3 study. The study will explore reproducibility of findings from previous FDA-regulated trials to further confirm the Phase 3 design. The brain imaging sub-study will explore the relationship between treatment outcomes of MDMA-assisted psychotherapy and brain function.
This Phase 2, open-label study assesses safety and effectiveness of MAP in participants with “at least severe” and “extreme” PTSD. Approximately 40 participants from research centres in Czech Republic, Finland, Germany, the Netherlands, Norway, Portugal and the UK are expected to join. In UK, Cardiff and SLaM will recruit patients. The study design is supported by Phase 2 pilot studies conducted by the Sponsor, which provide evidence that PTSD is treatable with 2-3 sessions of MAP and associated non-drug psychotherapy.
Participants receive 3 preparatory psychotherapy sessions, followed by an 8 week treatment period. MDMA is given with psychotherapy in 2 MAP sessions spaced approximately 1 month apart. Each MAP session is followed by 3 non-drug psychotherapy sessions. The primary outcome measure, the change in PTSD severity score, is assessed by an independent rater group.
Summary of Results
Study MP18, titled "An Open-Label, Phase 2, Multicenter Feasibility Study of Manualized MDMA-Assisted Psychotherapy with an Optional fMRI Sub-Study Assessing Changes in Brain Activity in Subjects with Posttraumatic Stress Disorder," was sponsored by MAPS Europe B.V. The research was done at 7 study centers in the United Kingdom, Germany, Norway, the Czech Republic, and the Netherlands from April 2021 to December 2023.
The goal of this study was to learn if two sessions of MDMA-assisted therapy is safe and helps lower symptoms in patients with severe posttraumatic stress disorder (PTSD). PTSD is a serious stress-related mental health condition that can happen after a person experiences a traumatic event. People with PTSD may experience nightmares, negative thoughts and feelings, intrusive thoughts, and may avoid places, people, activities, and things that remind them of the traumatic event. While there are treatments available for PTSD, they don't always work for everyone.
This study included 21 adult participants with severe PTSD. Participants completed 3 preparatory therapy sessions without any study drug, followed by 2 sessions of therapy with the study drug called MDMA, held approximately one month apart. After each MDMA-assisted therapy session, participants completed 3 more therapy sessions without any study drug. Participants were given a first dose of 80 mg MDMA HCl, followed by a supplemental half-dose 1.5-2 hours later of 40 mg MDMA HCl at the first session, and up to 120 mg MDMA HCl followed by a half-dose of 60 mg at the second session. Participants' PTSD symptoms were measured using a scale called the CAPS-5 at different timepoints throughout the study.
The study found that on average participants' CAPS-5 scores got lower at the end of the study, meaning their PTSD symptoms improved (CAPS-5 total scores went down by an average of 13.95 points).
The most common problems participants had after receiving the study drug were headache, nausea, and muscle tightness. Some participants also experienced thoughts about suicide, which can sometimes happen in patients with PTSD. Other problems that happened in at least 10% of participants included tiredness, anxiety, decreased appetite, difficulty sleeping, and muscle aches or pain. The majority of these problems were mild or moderate and went away on their own.
This study helped researchers understand that MDMA-assisted therapy may be generally safe and may help improve symptoms in patients with PTSD. However, this was a fairly small study and more research is needed.
More information about this study can be found on the EudraCT and clinicaltrials.gov clinical trial registries.
We greatly thank the study participants for their time, effort, and willingness to contribute to this research.
REC name
Wales REC 1
REC reference
20/WA/0099
Date of REC Opinion
19 May 2020
REC opinion
Further Information Favourable Opinion