MDMA-Assisted Exposure Therapy for PTSD

Overseen By Syreese Fuller

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Psychiatric medications, Concomitant medications

Disqualifiers: Substance abuse, Hypertension, Heart conditions, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 2 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people with PTSD by combining MDMA (also known as Ecstasy or Molly) with a type of therapy called Prolonged Exposure (PE). Researchers believe MDMA enhances feelings of connection and well-being, and when paired with PE, it may improve PTSD symptoms. Participants will receive MDMA during one of their therapy sessions in a 10-day program. This trial might suit those who currently have PTSD and are open to trying new treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that participants refrain from certain medications before the MDMA session. If you are on psychiatric medications, you may need to taper off under your local provider's guidance.

Is there any evidence suggesting that MDMA is likely to be safe for humans?

Research has shown that MDMA, when combined with therapy, is generally well-tolerated by people with PTSD. In one study, 83% of participants who received MDMA with therapy experienced an improvement in their PTSD symptoms. Importantly, the study found no serious side effects linked to the drug. This suggests that MDMA can be safe to use in therapy settings.

Another study found that MDMA-assisted therapy not only reduced PTSD symptoms but also improved daily life. These findings are encouraging for those considering participation in a clinical trial for MDMA therapy. However, it is always important to discuss potential risks with the trial team to determine if it is the right choice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about MDMA-assisted exposure therapy for PTSD because it offers a novel approach by combining a psychoactive compound, MDMA, with exposure therapy. Unlike traditional treatments like selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT), which often take weeks to months to show effectiveness, MDMA has the potential to enhance emotional processing and facilitate therapeutic breakthroughs more rapidly. This unique mechanism may help patients process traumatic memories with reduced fear and anxiety, potentially leading to quicker and more profound healing.

What evidence suggests that MDMA-assisted exposure therapy could be an effective treatment for PTSD?

Research has shown that therapy using MDMA can greatly reduce PTSD symptoms. In one study, 83% of participants who received MDMA therapy responded positively, compared to only 25% in the placebo group. Another study found that PTSD symptoms decreased significantly after MDMA treatment, with benefits lasting at least a year. MDMA may help by fostering feelings of closeness and empathy, enhancing the effectiveness of therapy sessions. Overall, MDMA-assisted therapy appears to be a promising and long-lasting option for people with PTSD. ^{1 2 6 7 8}

Who Is on the Research Team?

Jessica Maples-Keller, PhD

Principal Investigator

Emory University

Barbara O Rothbaum, PhD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals with PTSD who can swallow pills, have a support contact, and agree to lifestyle changes including fasting and avoiding certain medications. Women must test negative for pregnancy and use birth control. Participants cannot be in other clinical trials or have conditions that MDMA exacerbates, like uncontrolled hypertension or heart issues.

Inclusion Criteria

I agree to follow lifestyle changes, including fasting, avoiding certain meds, not joining other trials, and following study rules.

Willingness of the participant to sign a release for the investigators to communicate with their primary care or mental health providers if indicated

Are able to visually read and understand the English language and give written informed consent

Exclusion Criteria

Have uncontrolled hypertension documented on three separate occasions

I am unable to understand or sign the consent form.

I am currently on psychiatric medication but can consider tapering it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Phone screen and in-person assessment

Treatment

Participants undergo a 10-day Prolonged Exposure therapy program with MDMA administration on the second day

2 weeks

10 daily therapy sessions, including MDMA administration on Day 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Symptom assessments at 1, 2, and 4 weeks post-treatment via phone or online

What Are the Treatments Tested in This Trial?

Interventions

• MDMA

Trial Overview

The study tests the combination of MDMA with Prolonged Exposure therapy for treating PTSD over a 10-day program at Emory Brain Health Center. All participants receive MDMA on day two alongside daily PE sessions. The aim is to see if MDMA enhances the standard treatment's effectiveness.

How Is the Trial Designed?

Group I: Medicine Session Experimental Treatment 1 Intervention

3,4-methylenedioxymethamphetamine (MDMA) in combination with massed exposure therapy for PTSD

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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

MDMA-assisted psychotherapy has been recognized as a promising treatment for PTSD, receiving 'breakthrough therapy' status from the FDA in 2017, and is currently undergoing Phase III trials with potential approval expected in late 2023.

This treatment aims to address the limitations of existing PTSD therapies by combining the effects of MDMA with psychotherapy, although the article also highlights the need to consider risks and limitations in the current evidence base.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of MDMA-Assisted Therapy for Posttraumatic Stress Disorder. Lewis, BR., Byrne, K.[2023]

MDMA-assisted psychotherapy shows promise in reducing PTSD symptoms, with reductions in PTSD rating scores ranging from 23% to 68% in patients who did not respond to other treatments, although not all trials showed significant results and had methodological limitations.

MDMA alone, without accompanying psychotherapy, is unlikely to be effective, and there are potential adverse effects on blood pressure and heart rate, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3,4-Methylenedioxymethamphetamine's (MDMA's) Impact on Posttraumatic Stress Disorder. White, CM.[2019]

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 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]

The deuterium-substituted form of MDMA (d2-MDMA) shows similar effectiveness to MDMA in producing desired interoceptive effects, which are important for its therapeutic use in PTSD treatment.

d2-MDMA has a reduced potential for causing hyperthermia compared to MDMA, suggesting it may have a better safety profile while maintaining therapeutic benefits, warranting further research into its cardiovascular effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. Berquist, MD., Leth-Petersen, S., Kristensen, JL., et al.[2021]

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 phase 3 clinical trial with 90 participants suffering from severe PTSD, MDMA-assisted therapy significantly reduced PTSD symptoms compared to placebo, with a large effect size (d = 0.91).

The treatment was found to be safe and well-tolerated, showing no adverse events related to abuse potential or suicidality, suggesting it could be a promising new option for PTSD therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Mitchell, JM., Bogenschutz, M., Lilienstein, A., et al.[2023]

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.

pmc.ncbi.nlm.nih.gov

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

the first randomized controlled pilot study

The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse ...

3.

sciencedirect.com

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

assisted psychotherapy for posttraumatic stress disorder: A ...

MDMA-assisted psychotherapy appears to be a potentially safe, effective, and durable treatment for individuals with chronic, treatment-refractory PTSD.

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/29728331/

assisted psychotherapy for post-traumatic stress disorder in ...

PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 ...

5.

icer.org

icer.org/news-insights/press-releases/icer-releases-draft-evidence-report-on-treatment-for-post-traumatic-stress-disorder/

Institute for Clinical and Economic Review Releases Draft ...

While MDMA-AP may be a promising therapy for PTSD, functional unblinding in the clinical trials and additional concerns around trial design and ...

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.

7.

pubmed.ncbi.nlm.nih.gov

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

The safety and efficacy of {+/-}3,4- ...

Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all ...

8.

journals.plos.org

journals.plos.org/plosone/article?id=10.1371/journal.pone.0327778

MDMA-assisted therapy and current treatment options for ...

This systematic review suggests current treatments for PTSD are associated with heterogeneous evidence and the majority do not demonstrate sustained effects.