MDMA-Assisted Therapy for PTSD

(MDMA-PE Trial)

Overseen By Bettye Chargin

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Healing Breakthrough

Must not be taking: SSRIs, ADHD medications

Disqualifiers: Psychotic disorders, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 13

Duration: 3 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effects of MDMA (a psychoactive drug) combined with therapy on PTSD symptoms in veterans. It tests different doses of MDMA alongside therapy sessions to evaluate their effectiveness in reducing PTSD symptoms. Veterans diagnosed with PTSD who experience moderate symptoms might be suitable for this trial. Participants must be prepared for therapy and MDMA sessions, have someone to drive them home, and agree not to engage in other PTSD therapies during the study. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising treatment.

Will I have to stop taking my current medications?

The trial requires participants to refrain from certain medications before and after the MDMA session, including a possible tapering off of SSRIs and medications for ADHD. The protocol does not specify all medications that need to be stopped, so it's best to discuss your current medications with the study team.

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

Research has shown that MDMA-assisted therapy is generally safe. One study found that using MDMA with therapy is safe and effective for treating PTSD, with most participants experiencing no serious side effects. Another study found that most patients tolerated MDMA with therapy well, indicating that severe side effects were uncommon.

However, these results come from studies where health professionals carefully controlled and monitored doses. While MDMA has been shown to be safe in these settings, the exact doses used in the current study are not disclosed. Consulting a healthcare provider is always advisable to learn more about the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about MDMA-assisted therapy for PTSD because it introduces a novel approach that combines psychotherapy with the active ingredient MDMA, known for its potential to enhance emotional processing. Unlike traditional treatments such as selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy (CBT), this method directly involves a psychedelic compound that could help patients access and process traumatic memories more effectively. The treatment involves a unique combination of multiple non-medicine therapy sessions and a single session with MDMA, aiming to produce quicker and potentially more profound results in overcoming PTSD symptoms. This innovative technique offers hope for those who have not responded well to existing therapies.

What evidence suggests that this trial's treatments could be effective for PTSD?

Research has shown that therapy using MDMA can help reduce PTSD symptoms. In this trial, participants will receive either Dose A or Dose B of MDMA-assisted therapy. One study found that people who received MDMA with therapy had fewer PTSD symptoms than those who did not. Another study demonstrated that using MDMA with supportive therapy was safe and effective. Participants who took one or two doses of MDMA with therapy reported feeling better. These findings suggest that MDMA-assisted therapy could be a promising way to help people with PTSD. ^{1 2 3 4 6}

Who Is on the Research Team?

Leslie Morland, Psy.D.

Principal Investigator

San Diego Veterans Affairs Health System

Are You a Good Fit for This Trial?

This trial is for veterans aged 18 or older with PTSD from military events, who can speak and read English. Participants must be willing to take medication, attend therapy sessions, and have recordings made of these sessions. They need a designated driver post-MDMA session and a contact person in case of emergencies. Women capable of pregnancy must test negative and use reliable birth control.

Inclusion Criteria

Provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.

Be fluent in speaking and reading English.

Are willing to commit to medication dosing, therapy sessions, follow-up sessions, completing evaluation instruments, and all necessary telephone contact

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MDMA-assisted Massed Prolonged Exposure therapy, including 12 sessions of Prolonged Exposure and MDMA administration over 3 weeks

3 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including post-treatment follow-up CAPS-5 clinical interviews

4 months

Remote follow-up at 1 week, 2 months, and 4 months post-treatment

Optional Extension

Veterans in the low dose condition are offered an optional additional standard-dose MDMA session and up to three optional additional integration sessions

What Are the Treatments Tested in This Trial?

Interventions

• MDMA-assisted Massed Prolonged Exposure

Trial Overview The study tests the effect of MDMA-assisted prolonged exposure therapy on PTSD symptoms in veterans. It compares full-dose MDMA with low-dose MDMA to see which is more effective at reducing clinician-rated PTSD symptoms following the adapted Emory protocol.

How Is the Trial Designed?

Group I: Dose B (exact dose not disclosed) Experimental Treatment 2 Interventions

Non-medicine sessions of PE + One Medicine Session with 3,4-methylenedioxymethamphetamine (MDMA) PE Non-medicine sessions: 12 sessions MDMA Medicine session: Dose: exact dose not disclosed

Group II: Dose A (exact dose not disclosed) Experimental Treatment 2 Interventions

Non-medicine sessions of PE + One Medicine Session with 3,4-methylenedioxymethamphetamine (MDMA) PE Non-medicine sessions: 12 sessions MDMA Medicine session: Dose: exact dose not disclosed

MDMA-assisted Massed Prolonged Exposure is already approved in United States for the following indications:

Approved in United States as MDMA-assisted therapy for:

• Posttraumatic Stress Disorder (PTSD) - under investigation, not yet approved

Who Is Running the Clinical Trial?

Healing Breakthrough

Lead Sponsor

Trials

2

Recruited

30+

MAPS Public Benefit Corporation

Industry Sponsor

Trials

30

Recruited

900+

Lykos Therapeutics

Industry Sponsor

Trials

32

Recruited

960+

MAPS Public Benefit Corporation

Collaborator

Trials

2

Recruited

30+

National Center for PTSD

Collaborator

Trials

13

Recruited

1,200+

San Diego Veterans Healthcare System

Collaborator

Trials

38

Recruited

5,500+

White River Junction VA Medical Center

Collaborator

Trials

2

Recruited

110+

Published Research Related to This Trial

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]

MDMA-assisted psychotherapy (MDMA-AP) shows larger effect sizes in treating PTSD compared to prolonged exposure (PE) therapy, with clinician-observed outcomes at Hedges' g=1.17 versus g=1.08 for PE, indicating it may be more effective.

MDMA-AP also has a significantly lower dropout rate than PE therapy, suggesting that patients may find MDMA-AP more tolerable and acceptable as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy. Amoroso, T., Workman, M.[2018]

In a study involving 50 participants undergoing MDMA-assisted psychotherapy for PTSD, those who did not taper off their antidepressant medications showed significantly greater reductions in PTSD symptoms and depression severity compared to those who tapered their medications.

The results suggest that recent use of antidepressants may hinder the effectiveness of MDMA-assisted therapy, indicating the importance of medication management in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy. Feduccia, AA., Jerome, L., Mithoefer, MC., et al.[2021]

MDMA-assisted psychotherapy for treatment-resistant PTSD was found to be safe, with no serious adverse events reported during the trial involving 12 patients.

While there were no statistically significant reductions in PTSD symptoms measured by the Clinician-Administered PTSD Scale (CAPS), significant self-reported improvements were observed, and the effectiveness increased with more treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). Oehen, P., Traber, R., Widmer, V., et al.[2013]

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]

MDMA, used by over 16 million Americans, produces desirable effects like increased energy, elevated mood, and social bonding, but it also carries significant risks including liver damage, serotonin syndrome, and even death.

The drug's effects are influenced by its unique pharmacological profile and the rave environment, which can enhance both its positive and negative effects, highlighting the need for education and harm prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How MDMA's pharmacology and pharmacokinetics drive desired effects and harms. Michael White, C.[2019]

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]

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 shows promise in reducing psychological trauma for individuals with treatment-resistant PTSD, based on small-scale studies, but it is not yet established as a definitive treatment.

There is a critical need for accurate reporting and understanding of MDMA's role in therapy to prevent misconceptions that could hinder research and progress in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn't. Morgan, L.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06117306?intr=Midomafetamine%20&aggFilters=phase:3&rank=4

MDMA-assisted Massed Prolonged Exposure for PTSD The overall objective of this study is to pilot the VASDHS-adapted Emory MDMA-PE Protocol (aE-MDMA-PE) and assess the effect on clinician-rated PTSD symptoms in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8205851/

MDMA-assisted therapy for severe PTSD - PubMed Central Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1077722925000045

A Case Study of the METEMP Protocol: Massed Exposure ... MDMA combined with supportive therapy for PTSD is safe and effective. •. MDMA has not previously been combined with an evidence-based treatment. •. We ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05746572

NCT05746572 | MDMA Plus Exposure Therapy for PTSD Recent research combining one or two doses of MDMA with psychotherapy has shown improvements in PTSD symptoms. For the present study, the researchers will ...

5. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06117306

MDMA-assisted Massed Prolonged Exposure for PTSD The overall objective of this study is to pilot the VASDHS-adapted Emory MDMA-PE Protocol (aE-MDMA-PE) and assess the effect on clinician-rated PTSD symptoms in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6247454/

3,4-Methylenedioxymethamphetamine-assisted ... Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms.