MDMA-Assisted Therapy for PTSD

(MPVA6 Trial)

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests MDMA-assisted therapy to evaluate its effectiveness for U.S. military veterans with moderate chronic PTSD (post-traumatic stress disorder). The study compares the outcomes of two therapy sessions versus three to determine which is more beneficial. Participants will engage in several non-drug therapy sessions both before and after the MDMA-assisted ones. Veterans diagnosed with moderate PTSD who can commit to the study's requirements might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing veterans an opportunity to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MDMA-assisted therapy can be safe for people with PTSD. In earlier studies, no deaths or very serious side effects occurred, suggesting the treatment is generally safe for many with PTSD.

Another study found that MDMA-assisted therapy did not harm patients and was helpful for those who hadn't improved with other treatments. This suggests it can be a good option for people who haven't found relief with other therapies.

In summary, MDMA-assisted therapy appears well-tolerated and does not cause major harm. It is considered safe when administered in a controlled clinical setting. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MDMA-assisted therapy for PTSD because it offers a new way to tackle the condition. Unlike traditional treatments like SSRIs or cognitive behavioral therapy, MDMA works by enhancing emotional processing and reducing fear responses, allowing patients to engage more deeply in psychotherapy sessions. This unique combination of MDMA and therapy has the potential to provide quicker and possibly more effective relief from PTSD symptoms. Additionally, the therapy involves only two or three sessions, which could mean faster results compared to the weeks or months required by standard treatments.

What evidence suggests that this trial's treatments could be effective for PTSD?

Research shows that therapy with MDMA can greatly reduce PTSD symptoms. In this trial, participants will receive either two or three sessions of MDMA-assisted therapy. Studies have found that this treatment has led many patients to experience significant improvement or even remission of their PTSD. For instance, one study found that 71.2% of people who received MDMA-assisted therapy no longer had PTSD by the end of the trial. Other research also highlights major benefits, showing that PTSD symptoms improve when MDMA is used with therapy. Overall, these findings suggest that MDMA-assisted therapy could be a promising option for those dealing with PTSD. ^{2 6 7 8 9}

Who Is on the Research Team?

Rachel Yehuda

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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 can swallow pills.

Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. nature.com nature.com/articles/s41591-023-02565-4

MDMA-assisted therapy for moderate to severe PTSD These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34150406/

A Systematic Review and Meta-Analysis Findings show promising evidence for the potential therapeutic use of MDMA alongside psychotherapy in the treatment of PTSD.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11924292/

assisted psychotherapy in post-traumatic stress disorder: An ... Meta-analyses reported substantial benefits of MDMA-assisted psychotherapy in improving post-traumatic stress disorder symptoms.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584619301484

assisted psychotherapy for posttraumatic stress disorder: A ... MDMA-assisted psychotherapy demonstrated a high rate of clinical response (RR = 3.47, 95% CI: 1.70, 7.06), remission (RR = 2.63, 95% CI: 1.37, 5.02), with a ...

5. ucsf.edu ucsf.edu/news/2023/09/426116/mdmas-latest-trial-results-offer-hope-for-patients-ptsd

MDMA's Latest Trial Results Offer Hope for Patients with ... By the end of the 18-week trial period, 71.2% of the people in the MDMA-assisted therapy group no longer met the diagnostic criteria for PTSD, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3122379/

the first randomized controlled pilot study MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20643699/

The safety and efficacy of {+/-}3,4- ... MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178124003287

The efficacy and safety of MDMA-assisted psychotherapy ... This study aimed to systematically review and demonstrate the efficacy and safety of MDMA-assisted psychotherapy for the treatment of PTSD.

9. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20230681

MDMA and MDMA-Assisted Therapy | American Journal of ... A considerable body of preliminary evidence suggests that MDMA-AT delivered in a controlled clinical setting is a safe and efficacious treatment for PTSD.