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

Trial Summary

What is the purpose of this trial?

This is an open-label study of the use of MDMA Assisted Therapy for postpartum people with co-occurring Post Traumatic Stress Disorder (PTSD) and Opioid Use Disorder (OUD). The study protocol has been adapted from the Phase 3 studies sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS) for PTSD. Due to the high rate of concurrence of PTSD and OUD, people with OUD may experience great benefit from the treatment of their PTSD with MDMA-assisted therapy based on the phase 2 and 3 studies for PTSD. Use of MDMA-assisted therapy in this population has the potential to be of benefit for their OUD and maternal- infant attachment. 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 disorder. The CAPs 5 (PTSD) is the primary outcome, the Timeline Follow-Back (TLFB) for opioid use is the secondary outcome and other assessments of opioid use disorder, effects on maternal-infant attachment, social connectedness and other mental health outcomes are exploratory. The study will be conducted at the University of New Mexico Health Sciences Center located in Albuquerque New Mexico. In addition to northern New Mexico being an epicenter of the current opioid use disorder epidemic in the United States there is a long-standing history of multigenerational use of illicit opioids in many communities of northern New Mexico. There are high rates of opioid use disorder on pregnancy and accompanying Neonatal Opioid Use Withdrawal Syndrome (NOWS) in Albuquerque, Santa Fe, and surrounding communities.

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.

What data supports the effectiveness of the drug MDMA for PTSD and opioid use disorder?

Research shows that MDMA-assisted therapy significantly reduces PTSD symptoms and improves daily functioning, with studies indicating it is safe and well-tolerated even in people with other conditions like substance use disorders. ^{1 2 3 4 5}

Is MDMA-assisted therapy safe for humans?

Research shows that MDMA-assisted therapy is generally safe and well-tolerated in humans, even in those with severe PTSD and other conditions. Studies found no significant adverse events related to abuse potential, suicidality, or heart issues, and low doses were both psychologically and physically safe. ^{2 5 6 7 8}

How is MDMA-assisted therapy different from other treatments for PTSD and opioid use disorder?

MDMA-assisted therapy is unique because it combines the drug MDMA with psychotherapy, potentially enhancing the therapeutic process by affecting brain regions involved in PTSD. Unlike traditional treatments, MDMA acts as a catalyst in therapy, showing promise for those who haven't responded to other treatments. ^{4 6 7 9 10}

Research Team

Hadya Khawaja, MS, CIP

Principal Investigator

UNM Health Sciences Human Research Protections Program

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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 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]

References

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

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

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

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

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

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

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

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

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. 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]

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

A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. [2022]

10. 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]