MDMA Assisted Therapy for PTSD and Opioid Use Disorder

Overseen By Lawrence M Leeman, MD MPH

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of New Mexico

Must be taking: Methadone, Buprenorphine

Must not be taking: QT prolonging drugs

Disqualifiers: Psychotic disorder, Bipolar, Arrhythmia, 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: 8

Duration: 12 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether MDMA-assisted therapy can help individuals with both PTSD (a mental health condition triggered by a terrifying event) and opioid use disorder (OUD) after childbirth. The goal is to determine if treating PTSD with MDMA (also known as Ecstasy or Molly) can also benefit OUD and enhance the bond between mother and baby. Participants must have PTSD symptoms for at least three months, use methadone or buprenorphine for OUD, and be fluent in English. The trial focuses on the safety and effectiveness of this therapy in these specific conditions. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you must be stable on methadone or buprenorphine for at least 3 months. Additionally, you cannot use medications that prolong the QT/QTc interval during the experimental sessions.

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

Research has shown that MDMA-assisted therapy is well-tolerated by people with PTSD. Studies have demonstrated that MDMA can be safely administered in controlled environments. In earlier studies, participants did not experience serious harm when receiving MDMA-assisted therapy for PTSD. Common side effects included temporary increases in heart rate and blood pressure, as well as anxiety and fatigue, but these were usually mild and short-lived.

Another study found that MDMA-assisted therapy could help reduce PTSD symptoms, even when other treatments were ineffective. This suggests that the therapy could be beneficial and safe for people with PTSD and possibly for those with opioid use disorder (OUD) as well.

While the FDA has not yet approved MDMA for PTSD, ongoing research has shown promising safety results. The current trial phase indicates strong evidence supporting its safety, though more data is still needed to fully confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for PTSD and opioid use disorder, which often involve long-term medications like antidepressants or opioids replacement therapies, MDMA Assisted Therapy offers a novel approach by using MDMA as the active ingredient. This treatment is exciting because MDMA works differently; it enhances emotional processing and reduces fear, potentially allowing patients to confront and work through traumatic memories more effectively. Additionally, the therapy involves only a few sessions, which could lead to faster improvements compared to conventional treatments requiring ongoing medication. Researchers are particularly hopeful that this method might offer significant benefits for individuals with co-occurring PTSD and opioid use disorder by addressing both conditions simultaneously.

What evidence suggests that MDMA-assisted therapy might be an effective treatment for PTSD and opioid use disorder?

Research has shown that therapy using MDMA, which participants in this trial will receive, can greatly reduce PTSD symptoms, even for those who haven't found relief with other treatments. In one study, 83% of people who received MDMA showed improvement, compared to just 25% who received a placebo. MDMA increases certain brain chemicals like serotonin and oxytocin, which can lift mood and enhance feelings of connection. This therapy also appears to strengthen the bond between mothers and their babies, which is important for new mothers. Although limited data exists on how this therapy affects opioid use disorder (OUD), successfully treating PTSD might also help with OUD symptoms because the two conditions are often linked. ^{1 2 3 4 5}

Who Is on the Research Team?

Hadya Khawaja, MS, CIP

Principal Investigator

UNM Health Sciences Human Research Protections Program

Are You a Good Fit for This Trial?

This trial is for postpartum individuals at least 18 years old with PTSD and OUD, using a stable dose of methadone or buprenorphine. Participants must speak English, be able to swallow pills, consent to recorded sessions, provide an emergency contact, inform investigators about medical changes, and use effective birth control if applicable.

Inclusion Criteria

I am not pregnant and agree to use birth control during the study.

Participants must be able to swallow pills

Participants must provide a contact person who is willing and able to be reached in case of emergencies

Exclusion Criteria

I am unable to understand or sign the consent form.

Prisoners

Participants likely to be re-exposed to their index trauma, lack social support, or lack a stable living situation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preparatory

Medication tapering, preparatory sessions, and baseline assessments

3-4 weeks

2-3 visits (in-person)

Treatment

Three monthly MDMA-assisted therapy sessions with integrative sessions

12 weeks

3 visits (in-person) for MDMA sessions, 3 visits (in-person) for integrative sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• MDMA

Trial Overview The study tests MDMA Assisted Therapy's feasibility and safety in treating PTSD in those with OUD after childbirth. It adapts from Phase 3 studies by MAPS for PTSD treatment. Outcomes include the CAPs 5 for PTSD and TLFB for opioid use; other mental health outcomes are also explored.

How Is the Trial Designed?

Group I: Co-occurring PTSD and OUD prior and after treatment with MDMA Assisted Therapy Experimental Treatment 1 Intervention

The intervention is MDMA Assisted Therapy focused on PTSD and three experiment sessions with the first session using an initial dose of 100 mg MDMA HCL (\~80 mg MDMA) with supplemental dose of 40 mg MDMA HCL (\~35 mg MDMA). Total dose range for the first session is 100 mg MDMA HCL (\~80 mg MDMA) to 140 mg MDMA HCL (\~115 mg MDMA).The second and third sessions may use an initial dose of 120 mg MDMA HCL (\~100 mg MDMA) with a supplemental dose of 60 mg MDMA HCL (\~50 mg MDMA) for a total dose range of 120 mg MDMA HCL (\~100 mg MDMA) to 180 mg MDMA HCL (\~160 mg MDMA) Total cumulative dose range for the three sessions is 340mg MDMA HCL (\~280 mg MDMA) to 500 mg MDMA HCL (\~435 mg MDMA)

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?

University of New Mexico

Lead Sponsor

Trials

393

Recruited

3,526,000+

Lykos Therapeutics

Collaborator

Trials

12

Recruited

330+

Multidisciplinary Association for Psychedelic Studies

Collaborator

Trials

40

Recruited

1,200+

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]

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) and a mean CAPS-5 score change of -24.4 in the MDMA group.

The treatment was found to be safe and well-tolerated, showing no adverse events related to abuse potential, suicidality, or QT prolongation, even among participants with common comorbidities.

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]

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]

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 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]

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]

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, once used as a therapeutic aid before being classified as a Schedule I drug in 1985, has shown promise in treating posttraumatic stress disorder (PTSD) when used in psychotherapy, despite limited research due to its scheduling.

The review highlights the brain regions affected by both PTSD and MDMA, such as the amygdala and hippocampus, suggesting that MDMA may work through specific neurochemical mechanisms to enhance therapeutic outcomes in PTSD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Psychopharmacology of ±3,4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder. Amoroso, T.[2015]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05219175

MDMA for Co-occurring PTSD and OUD After Childbirth This study will serve to explore the feasibility and safety of offering MDMA-assisted therapy for treatment of PTSD in postpartum people with opioid use ...

3. 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 ...

4. icer.org icer.org/wp-content/uploads/2023/11/PTSD_Revised-Report_For-Publication_05142024.pdf

Midomafetamine-Assisted Psychotherapy for Post- ... Additionally, we evaluated available evidence on the comparative effectiveness of MDMA-AP versus other short-term trauma-focused psychotherapies ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178124003287

The efficacy and safety of MDMA-assisted psychotherapy ... The results revealed that MDMA-assisted psychotherapy effectively reduced the change from baseline score in the Clinician-Administered PTSD Scale in patients ...