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

Trial Summary

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.

What data supports the effectiveness of the drug MDMA for PTSD?

Research shows that MDMA-assisted therapy significantly reduces PTSD symptoms compared to a placebo, with 83% of patients showing improvement. The U.S. FDA has recognized its potential by granting it 'breakthrough therapy' status, and ongoing studies suggest it may soon be approved for PTSD treatment. ^{1 2 3 4 5}

Is MDMA-assisted therapy safe for humans?

MDMA-assisted therapy has been found to be generally safe in controlled settings, though it can increase blood pressure, heart rate, and body temperature. Low doses have been shown to be both psychologically and physiologically safe in small studies, but more research is needed to confirm safety in larger groups. ^{1 4 6 7 8}

How is the drug MDMA used in treating PTSD different from other treatments?

MDMA-assisted therapy is unique because it combines the drug MDMA with psychotherapy, which can enhance the therapeutic process by reducing fear and defensiveness, allowing patients to process traumatic memories more effectively. This approach is particularly promising for those with PTSD who have not responded to traditional treatments. ^{1 2 3 6 9}

What is the purpose of this trial?

Posttraumatic stress disorder (PTSD) is a debilitating disorder. While effective treatments exist, some patients fail to receive the full benefits. Alternative treatment approaches are needed. 3,4-methylenedioxymethamphetamine (MDMA) is a medicine associated with feelings of closeness and love for others, empathy, insightfulness, and feelings of peace or well-being. Recent research combining one or two doses of MDMA with psychotherapy has shown improvements in PTSD symptoms. For the present study, the researchers will investigate MDMA in combination with Prolonged Exposure therapy (PE), a gold-standard treatment for PTSD. All participants receive MDMA on the second day of a 10-day PE treatment program in which a PE therapy session occurs each day. This study will occur at the Emory Brain Health Center. Potential participants will be recruited via community advertising and mental health referrals. The research team will also collect psychophysiological data for exploratory analyses regarding how MDMA may improve PE treatment for PTSD. This is an important study as it is the first time MDMA will be combined with an evidence-based existing PTSD treatment. The study population will consist of people who meet the criteria for PTSD and are medically appropriate for MDMA administration.

Research Team

Jessica Maples-Keller, PhD

Principal Investigator

Emory University

Barbara O Rothbaum, PhD

Principal Investigator

Emory University

Eligibility Criteria

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.

Have previously participated in a Multidisciplinary Association for Psychedelic Studies (MAPS) sponsored MDMA clinical trial

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

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 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]

References

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

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

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 Review of MDMA-Assisted Therapy for Posttraumatic Stress Disorder. [2023]

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

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. [2023]

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

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

7. Ireland pubmed.ncbi.nlm.nih.gov

In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. [2021]

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. Germany pubmed.ncbi.nlm.nih.gov

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