Group MDMA Therapy for PTSD

(Group-MVP Trial)

Overseen By Kevin Rothstein-Kightly, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Portland VA Research Foundation, Inc

Disqualifiers: Uncontrolled hypertension, Significant medical disorders, others

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

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and potential benefits of using MDMA, a psychoactive drug, in group therapy sessions to treat PTSD (post-traumatic stress disorder) in veterans. Participants will engage in group therapy sessions, both with and without MDMA, to determine its effect on PTSD symptoms. Veterans with a current PTSD diagnosis who can attend sessions and follow medication instructions may be suitable candidates for this trial. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering veterans a chance to contribute to groundbreaking PTSD treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must commit to the study's medication dosing and procedures, so it's best to discuss your current medications with the study team.

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

Research has shown that MDMA-assisted therapy can be administered to people with PTSD without causing harm. In several studies, patients who received MDMA treatment did not experience major negative effects, indicating the treatment was generally well-tolerated.

One study found that MDMA-assisted therapy helped reduce PTSD symptoms and was considered safe for most people. However, like any treatment, some risks or side effects may still exist. Always discuss any concerns with the research team or a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for PTSD?

Most treatments for PTSD, like cognitive behavioral therapy (CBT) and antidepressants, focus on managing symptoms over time. But MDMA-assisted group therapy works differently by using MDMA to enhance emotional openness and connection during therapy sessions. This unique approach aims to help patients process traumatic memories more deeply and effectively. Researchers are excited because MDMA has the potential to accelerate healing, possibly offering relief in a shorter time frame compared to traditional treatments.

What evidence suggests that MDMA-assisted group therapy is effective for PTSD?

Research has shown that therapy using MDMA can help treat PTSD. In one study, 71.2% of participants no longer had PTSD after 18 weeks of MDMA treatment. Another study found that MDMA can ease PTSD symptoms, even in severe cases, by boosting brain chemicals like dopamine and serotonin. In this trial, participants will receive MDMA-assisted group therapy, which has been shown to lessen PTSD symptoms and their negative effects on daily life. These promising results suggest that MDMA-assisted therapy could be a strong option for those dealing with PTSD. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for U.S. Military Veterans aged 18 or older with PTSD who can swallow pills, agree to recorded study visits, and commit to the study's procedures. Participants must not be in other trials, have a reliable emergency contact, and if capable of pregnancy, use contraception and provide negative tests.

Inclusion Criteria

Must agree to inform the investigators within 48 hours of any medical conditions and procedures

Must provide a contact who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable

If able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate contraception through 10 days after the last Experimental Session

Exclusion Criteria

I am unable to understand or sign the consent form.

I have symptoms related to liver or bile duct problems.

Have a marked baseline QTcF interval >450 milliseconds [ms] demonstrated on repeated ECG assessments

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Sessions

Participants undergo four preparatory therapy sessions before MDMA sessions

4 weeks

4 visits (in-person)

MDMA Sessions

Participants receive two once-monthly open-label MDMA sessions

2 months

2 visits (in-person)

Integrative Sessions

Participants undergo four integrative therapy sessions following each MDMA session

2 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Group Therapy
• MDMA

Trial Overview The trial explores MDMA-assisted group therapy for treating PTSD in veterans. It involves three cohorts of six participants each undergoing therapy sessions together without random assignment to different treatments (open-label).

How Is the Trial Designed?

Group I: MDMA-assisted group therapy Experimental Treatment 2 Interventions

Four Preparatory Sessions, two MDMA Sessions, and four Integrative Sessions following each MDMA Session.

Group Therapy is already approved in United States for the following indications:

Approved in United States as Group Therapy for:

• Tertiary prevention of child sexual abuse

Who Is Running the Clinical Trial?

Portland VA Research Foundation, Inc

Lead Sponsor

Trials

2

Recruited

50+

Steven & Alexandra Cohen Foundation

Collaborator

Trials

10

Recruited

320+

Steven & Alexandra Cohen Foundation

Collaborator

Trials

5

Recruited

150+

Published Research Related to This Trial

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-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]

In a small study of six women with chronic PTSD due to sexual assault, low doses of MDMA (50-75 mg) were found to be safe both psychologically and physiologically.

The study highlights the need for further research with larger sample sizes and higher doses to better understand the safety and efficacy of MDMA-assisted psychotherapy for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. Bouso, JC., Doblin, R., Farré, M., et al.[2013]

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]

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]

In a study involving six couples where one partner had PTSD, MDMA-facilitated cognitive-behavioral conjoint therapy (CBCT) showed significant improvements in PTSD symptoms and relationship satisfaction, with effect sizes ranging from 1.85 to 3.59.

The treatment was safe and well-tolerated, with no serious adverse events reported, suggesting that MDMA can enhance the effectiveness of therapy for both individual and relational functioning in PTSD cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial. Monson, CM., Wagner, AC., Mithoefer, AT., et al.[2021]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10660711/

MDMA-Based Psychotherapy in Treatment-Resistant Post ... MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, ie, dopamine, serotonin, norepinephrine, and oxytocin.

2. 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1077722925000227

MDMA-Assisted Group Therapy for PTSD: Development of ... This paper describes a novel protocol for group-based MDMA-assisted therapy for veterans with PTSD. This single-arm, open-label study will focus on feasibility ...

4. 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, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01793610

Dose-Response Study of MDMA-assisted Psychotherapy ... The goal of this clinical trial is to learn if MDMA in combination with therapy is safe and effective in people with chronic, treatment-resistant 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. icer.org icer.org/wp-content/uploads/2023/11/PTSD_Revised-Report_For-Publication_05142024.pdf

Midomafetamine-Assisted Psychotherapy for Post- ... A greater mean reduction in modified SDS score was seen with MDMA-AP than LSNAP (-1.5; 95% CI: -1.6 to -1.4). There is no established threshold ...