MDMA-Assisted Therapy for PTSD

(MPVA6 Trial)

Overseen By Recruitment Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: MAPS Public Benefit Corporation

Disqualifiers: Uncontrolled hypertension, Significant medical disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: 8-12 weeks

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the effectiveness of different numbers of MDMA-assisted therapy sessions in U.S. military veterans with moderate to severe PTSD. MDMA helps patients feel more open and comfortable during therapy, aiding in the processing of traumatic memories. MDMA-assisted psychotherapy began in the 1980s but was shelved due to public health concerns.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug MDMA-assisted therapy for PTSD?

Research shows that MDMA-assisted therapy significantly reduces PTSD symptoms compared to a placebo, with 83% of patients showing improvement. Additionally, MDMA-assisted therapy has larger effect sizes and lower dropout rates compared to traditional prolonged exposure therapy, suggesting it is a promising treatment for PTSD. ^{1 2 3 4 5}

Is MDMA-assisted therapy safe for humans?

MDMA-assisted therapy has been shown to be safely administered in clinical settings for PTSD, with no serious drug-related adverse events reported in trials. However, there is a potential risk of serotonin syndrome (a condition caused by too much serotonin in the brain) if MDMA is taken with other substances that affect serotonin. ^{2 4 5 6 7}

How is MDMA-assisted therapy different from other PTSD treatments?

MDMA-assisted therapy is unique because it combines the drug MDMA with psychotherapy to enhance the effectiveness of talk therapy for PTSD, especially in patients who haven't responded to other treatments. Unlike traditional therapies, MDMA may help reduce fear and defensiveness, allowing patients to process traumatic memories more effectively. ^{1 2 4 5 8}

Research Team

Rachel Yehuda

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for U.S. military veterans aged 18 or older with moderate chronic PTSD. Participants must not be in other trials, able to swallow pills, and fluent in the study site's language. They need a contact person in case of emergencies and agree to recorded sessions and overnight stays post-treatment.

Inclusion Criteria

You are not participating in any other interventional clinical trials during the duration of the study.

I am 18 years old or older.

I can swallow pills.

Exclusion Criteria

I have had low sodium levels or very high body temperature in the past.

You have a history of serious medical conditions or currently have a significant medical problem.

I have symptoms caused by liver problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Sessions

Participants undergo three non-drug preparatory sessions prior to their first MDMA-assisted therapy session

3 weeks

3 visits (in-person)

Treatment

Participants receive 2 or 3 MDMA-assisted therapy sessions, each followed by three non-drug integrative therapy sessions

8-12 weeks

6-9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MDMA
• Psychotherapy

Trial Overview The study compares the effectiveness of two versus three active MDMA-assisted psychotherapy sessions for treating PTSD in veterans. It's an open-label, randomized trial where participants will receive either two or three doses of MDMA during therapy at a VA clinic.

Participant Groups

Group I: Two sessions of MDMA-assisted therapy Active Control 2 Interventions

Two experimental sessions of MDMA-assisted therapy

Group II: Three sessions of MDMA-assisted therapy Active Control 2 Interventions

Three experimental sessions of MDMA-assisted therapy

MDMA is already approved in United States for the following indications:

Approved in United States as MDMA for:

• Posttraumatic stress disorder (PTSD)

Who Is Running the Clinical Trial?

MAPS Public Benefit Corporation

Lead Sponsor

Trials

30

Recruited

900+

Lykos Therapeutics

Lead Sponsor

Trials

32

Recruited

960+

Multidisciplinary Association for Psychedelic Studies

Lead Sponsor

Trials

40

Recruited

1,200+

Findings from Research

In a clinical trial involving 20 patients with chronic PTSD who had not responded to other treatments, those receiving MDMA during psychotherapy showed a significantly greater reduction in PTSD symptoms compared to the placebo group, with an 83% response rate in the MDMA group versus 25% in the placebo group.

MDMA-assisted psychotherapy was found to be safe, with no serious adverse events or negative effects on neurocognitive function, suggesting it could be a beneficial treatment option for patients with treatment-resistant PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Mithoefer, MC., Wagner, MT., Mithoefer, AT., et al.[2021]

MDMA-assisted psychotherapy for treatment-resistant PTSD was found to be safe, with no serious adverse events reported during the trial involving 12 patients.

While there were no statistically significant reductions in PTSD symptoms measured by the Clinician-Administered PTSD Scale (CAPS), significant self-reported improvements were observed, and the effectiveness increased with more treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). Oehen, P., Traber, R., Widmer, V., et al.[2013]

MDMA-assisted psychotherapy (MDMA-AP) shows larger effect sizes in treating PTSD compared to prolonged exposure (PE) therapy, with clinician-observed outcomes at Hedges' g=1.17 versus g=1.08 for PE, indicating it may be more effective.

MDMA-AP also has a significantly lower dropout rate than PE therapy, suggesting that patients may find MDMA-AP more tolerable and acceptable as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy. Amoroso, T., Workman, M.[2018]

MDMA-assisted psychotherapy shows significant reductions in PTSD symptoms, as measured by the Clinician Administered PTSD Scale (CAPS-IV), particularly at doses of 75 mg and 125 mg, based on a meta-analysis of four randomized controlled trials involving treatment-resistant PTSD patients.

While MDMA treatment was associated with some adverse effects like low mood and nausea, the overall risk was minimal, suggesting that MDMA could be a promising option for patients who have not responded to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. Illingworth, BJ., Lewis, DJ., Lambarth, AT., et al.[2022]

An estimated 0.9% of individuals aged 12 and older in the U.S. reported using ecstasy/MDMA in the past year, indicating that while use is relatively rare, it is more common among younger age groups and certain racial minorities.

Factors such as past-year use of other drugs, prescription drug misuse, nicotine dependence, and alcohol use disorder were associated with increased odds of ecstasy/MDMA use, highlighting the need for targeted prevention and harm reduction strategies for at-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Correlates of Past Year Ecstasy/MDMA Use in the United States. Yang, KH., Kepner, W., Nijum, A., et al.[2023]

MDMA is being studied as a potential treatment for post-traumatic stress disorder (PTSD) and anxiety-related conditions, with promising results leading to expected FDA approval in the near future.

In a review of adverse events, no cases of serotonin syndrome (SS) were reported in clinical trials where MDMA was the only substance taken, suggesting that MDMA may be safe when used alone, although caution is warranted when combined with other serotonergic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. Makunts, T., Jerome, L., Abagyan, R., et al.[2022]

A systematic review of 16 studies and a meta-analysis of 10 studies involving 168 patients suggest that MDMA, when used in conjunction with psychotherapy, shows promising efficacy in treating post-traumatic stress disorder (PTSD).

The analysis highlights both the potential benefits and adverse events associated with MDMA treatment, indicating that it may be particularly beneficial for treatment-resistant patients, thus paving the way for future drug development in psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of MDMA (3,4-Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta-Analysis. Tedesco, S., Gajaram, G., Chida, S., et al.[2021]

In a study involving 39 healthy adults, MDMA did not reduce physiological or subjective stress responses during a public speaking task, contrary to the hypothesis that it would dampen stress reactions.

While MDMA is known for its potential benefits in treating PTSD, this research indicates that a single dose does not moderate acute stress responses, suggesting that its therapeutic effects may depend on different conditions or contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDMA does not alter responses to the Trier Social Stress Test in humans. Bershad, AK., Miller, MA., de Wit, H.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Prevalence and Correlates of Past Year Ecstasy/MDMA Use in the United States. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

The Efficacy of MDMA (3,4-Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta-Analysis. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

MDMA does not alter responses to the Trier Social Stress Test in humans. [2018]