MDMA-Assisted Therapy for Post-Traumatic Stress Disorder

Not yet recruiting at 1 trial location

Overseen By Christy Capone, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: VA Office of Research and Development

Must not be taking: Antidepressants, Antipsychotics, others

Disqualifiers: Uncontrolled hypertension, Liver disease, Seizures, 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: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of MDMA-assisted therapy for military veterans with both PTSD (a mental health condition triggered by traumatic events) and Alcohol Use Disorder. The study compares full-dose MDMA therapy to a low-dose, placebo-controlled version to assess their effects on PTSD symptoms and drinking habits. Veterans who have tried other PTSD treatments, have experienced PTSD symptoms for at least six months, and can abstain from alcohol for 48 hours may be suitable candidates. As a Phase 2/3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering veterans a chance to contribute to potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, such as antidepressants and antipsychotics, before joining. There is a specific 'washout' period (time without taking certain medications) for antidepressants, which is 5 half-lives plus 1 week.

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

Research shows that MDMA-assisted therapy can be safe and helpful for people with PTSD. Previous studies reported no deaths or serious side effects. Although some participants experienced suicidal thoughts or behavior, these instances were rare. MDMA used in therapy has helped reduce PTSD symptoms and improve daily life. Prospective participants should know that most past participants handled the treatment well, with healthcare professionals closely monitoring them. ^{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 unique approach compared to traditional treatments like psychotherapy and antidepressants. Unlike these standard options, MDMA works by enhancing emotional processing and increasing feelings of trust and empathy during therapy sessions, potentially leading to deeper healing. The therapy involves a combination of MDMA doses and psychological support, which might help patients access and process traumatic memories more effectively. Additionally, while conventional treatments can take weeks or months to show significant results, MDMA-assisted therapy has the potential to provide noticeable benefits after just a few sessions.

What evidence suggests that this trial's treatments could be effective for PTSD and AUD in military Veterans?

Research has shown that therapy using MDMA can greatly reduce PTSD symptoms. In one study, 67% to 71% of participants no longer had PTSD after completing the therapy. MDMA boosts brain chemicals like dopamine and oxytocin, which can lift mood and improve social connections. Other studies have found that MDMA therapy not only eases PTSD symptoms but also enhances overall functioning and quality of life. In this trial, participants will receive either a full dose of MDMA or an active placebo dose as part of the MDMA-assisted therapy. While this treatment mainly targets PTSD, the current trial also explores its effects on alcohol use disorder in veterans. ^{1 2 3 4 6}

Who Is on the Research Team?

Erica M. Eaton, PhD

Principal Investigator

Providence VA Medical Center, Providence, RI

Are You a Good Fit for This Trial?

This trial is for military veterans who have both PTSD and Alcohol Use Disorder. Participants must be diagnosed with these conditions to qualify. The study excludes individuals who don't meet the specific diagnostic criteria or have other health issues that could interfere with the treatment or skew the results.

Inclusion Criteria

Participants must be currently enrolled in VA care

Participants must be fluent in speaking and reading English

Participants must be able to swallow pills

Exclusion Criteria

Participants with significant alcohol withdrawal symptoms are excluded

Participants with a recent history of clinically significant hyponatremia or hyperthermia are excluded

Participants with a marked Baseline QTcF interval >450 ms demonstrated on repeated ECG assessments are excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants engage in MDMA-assisted therapy or identical psychotherapy with low dose MDMA over three once-monthly Experimental Sessions

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at post-treatment, 3-, and 6-month follow-ups

22 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active Placebo Dose MDMA
• Full Dose MDMA
• MDMA-Assisted Therapy

Trial Overview The trial tests MDMA-assisted therapy (MDMA-AT) versus a low-dose active placebo combined with psychotherapy, specifically targeting veterans with PTSD and AUD. It aims to see if full-dose MDMA can improve PTSD symptoms and reduce alcohol consumption more effectively than a lower dose.

How Is the Trial Designed?

Group I: Full dose MDMA-Assisted Therapy Experimental Treatment 2 Interventions

Initial dose of 80 mg MDMA HCl administered orally at the start of each of three dosing sessions, possibly followed by a supplemental dose of 40 mg MDMA HCl 1.5 to 2 hours later. At dosing sessions 2 and 3, participants will be offered the option of taking a higher dose, 120 mg MDMA HCl, possibly followed by a supplemental dose of 60 mg MDMA HCl 1.5 to 2 hours later.

Group II: Active Placebo dose MDMA-Assisted Therapy Active Control 2 Interventions

During the three Experimental Sessions, participants will receive the active placebo dose (one capsule) consisting of 40 mg MDMA HCl plus a second capsule containing an inactive placebo (indistinguishable weight placebo comprised entirely of mannitol and magnesium stearate), followed 1.5-2 hours later by the inactive placebo. The number of capsules comprising the initial dose (two) is consistent across both conditions.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

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

MDMA and MDMA-Assisted Therapy | American Journal of ... After a course of MDMA-AT involving three MDMA administrations supported by psychotherapy, 67%–71% of individuals with PTSD no longer meet ...

4. 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.

5. tandfonline.com tandfonline.com/doi/full/10.1080/02791072.2025.2577308?src=

Full article: MDMA-Assisted Psychotherapy for PTSD Of the six studies included in the efficacy analysis, five (83.3%) found significantly improved PTSD symptoms in the MDMA groups compared to ...

6. 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.