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

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This Phase 2a, open-label, non-randomized, 3-cohort study assesses the feasibility and safety of MDMA-assisted group therapy for the treatment of PTSD in veterans. The study will be conducted in up to N=18 participants, recruited in three cohorts of six participants each and receive therapy sessions throughout their participation in these group cohorts.

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 MDMA safe for use in group therapy for PTSD?

Preliminary studies suggest that low doses of MDMA are both psychologically and physically safe for use in therapy for PTSD, but more research with larger groups is needed to confirm this. ^{1 2 3 4 5}

How does MDMA-assisted group therapy differ from other PTSD treatments?

MDMA-assisted group therapy for PTSD is unique because it combines the effects of MDMA, a drug known for its ability to reduce fear and enhance emotional openness, with group therapy, potentially enhancing the therapeutic process and outcomes for those who have not responded to traditional treatments. ^{1 2 3 6 7}

What data supports the effectiveness of the drug MDMA in treating PTSD?

Research shows that MDMA-assisted therapy can significantly reduce PTSD symptoms, with studies indicating it has larger effects than traditional therapies and lower dropout rates. Patients receiving MDMA therapy reported significant improvements in PTSD symptoms and personal growth, with no serious side effects. ^{3 6 8 9 10}

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.

My high blood pressure is not under control.

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

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]

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]

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]

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 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]

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 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]

Citations

1. 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]

2. 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]

3. 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]

4. 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]

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

Posttraumatic Growth After MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

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

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

MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. [2013]

9. 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]

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

MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial. [2021]