MDMA-Assisted Psychotherapy for PTSD

Overseen By Anne Wagner, C.Psych.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Remedy

Must not be taking: Psychiatric medications, Ketamine, Ecstasy, others

Disqualifiers: Pregnancy, Psychotic disorders, Heart disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 7 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining MDMA (a psychoactive drug also known as Ecstasy) with Cognitive-Behavioral Conjoint Therapy (CBCT) benefits people with Post-Traumatic Stress Disorder (PTSD) more than therapy alone. PTSD can complicate daily life and relationships, and the study examines if MDMA can enhance therapy by reducing fear and improving communication and empathy. The trial includes two groups: one will receive CBCT with MDMA sessions, and the other will have CBCT only, with an opportunity to try MDMA later. This trial suits those in the Greater Toronto Area with PTSD and a close person willing to participate with them. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

Yes, participants must stop taking psychiatric medications, herbal supplements, and both prescription and nonprescription medications during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that MDMA therapy has potential in alleviating PTSD symptoms. Studies have found that MDMA, when used in therapy, can reduce PTSD symptoms and improve functioning. Most patients tolerate it well. Some may experience temporary side effects like a faster heartbeat, higher blood pressure, or anxiety, but these are usually mild and manageable. Importantly, extensive research continues to enhance understanding of its safety.

For those considering joining a trial, MDMA-assisted therapy could be a safe option. However, discussing any concerns with the trial team or a healthcare professional is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MDMA-assisted CBCT for PTSD because it introduces MDMA as a novel element in psychotherapy, potentially enhancing emotional processing and connection during therapy. Unlike traditional treatments that often focus solely on talk therapy or medications like SSRIs, MDMA-assisted therapy combines both pharmacological and psychological approaches. This integration could lead to more significant and faster relief from PTSD symptoms by allowing patients to process traumatic memories in a supportive and empathetic state. Additionally, the option for a crossover to include MDMA sessions after initial therapy may offer an added layer of flexibility and effectiveness for patients who do not respond to conventional methods alone.

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

Research has shown that therapy using MDMA yields promising results in reducing PTSD symptoms. One study demonstrated significant improvement, with 5 out of 6 patients experiencing lasting relief from PTSD for six months. MDMA aids by reducing fear and enhancing communication and empathy, thereby making therapy more effective. The FDA has recognized the potential benefits of MDMA-assisted therapy by granting it breakthrough therapy status. In this trial, participants in the MDMA-Assisted CBCT Condition will receive MDMA integrated into their psychotherapy sessions, while those in the CBCT-Only Condition will undergo psychotherapy without MDMA. These findings suggest that combining MDMA with therapy might be more effective for treating PTSD than therapy alone. ^{1 2 3 4 6}

Who Is on the Research Team?

Paul Uy, MD

Principal Investigator

Remedy Institute

Anne Wagner, PhD

Principal Investigator

Remedy Institute

Are You a Good Fit for This Trial?

This trial is for adults with PTSD in the Greater Toronto Area who are willing to stop taking certain medications and agree to study rules. Participants must be healthy, able to swallow pills, proficient in English, and have a supportive person willing to join the study. Pregnant individuals or those at risk of becoming pregnant without contraception are excluded.

Inclusion Criteria

You are an Ontario resident residing in the Greater Toronto Area.

You possess fluency in both spoken and written English.

You have consented to the study's regulations and are willing to attend all medical and treatment appointments.

Exclusion Criteria

I am unable to understand or sign the consent form.

I have an underactive thyroid and am not taking medication for it.

I can follow the study's schedule and rules.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 7-week course of CBCT psychotherapy, with the MDMA-assisted group receiving two MDMA sessions as an adjunct to therapy

7 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including self-compassion, social support, PTSD symptoms, and relationship satisfaction

3 months

Crossover (optional)

Participants in the CBCT-only condition have the option to crossover and receive two MDMA sessions after follow-up

What Are the Treatments Tested in This Trial?

Interventions

• CBCT
• CBCT RCT
• MDMA-Assisted CBCT for PTSD

Trial Overview The trial tests MDMA-assisted Cognitive-Behavioral Conjoint Therapy (CBCT) against CBCT alone for PTSD treatment. It explores whether MDMA's effects on empathy and openness can enhance CBCT's impact on symptoms and relationship satisfaction over a 7-week course with two full-day sessions.

How Is the Trial Designed?

Group I: MDMA-Assisted CBCT Condition Experimental Treatment 1 Intervention

Dyads will undergo a 7-week course of CBCT psychotherapy for PTSD with two sessions that integrate MDMA-assisted psychotherapy. MDMA will be administered in two separate sessions and integrated into the psychotherapy protocol. The two doses of MDMA during this study will be used as an adjunct to psychotherapy.

Group II: CBCT-Only Condition Active Control 1 Intervention

Dyads will undergo a 7-week course of CBCT psychotherapy for PTSD. Dyads who have undergone the CBCT-Only condition will have the option to do a crossover and have the two MDMA sessions after follow-up.

CBCT is already approved in United States, European Union for the following indications:

Approved in United States as MDMA for:

• Post-Traumatic Stress Disorder (PTSD) - Investigational

Approved in European Union as MDMA for:

• Post-Traumatic Stress Disorder (PTSD) - Investigational

Who Is Running the Clinical Trial?

Remedy

Lead Sponsor

Trials

3

Recruited

220+

Remedy Institute

Collaborator

Trials

1

Recruited

60+

Published Research Related to This Trial

In a phase 2 trial involving 26 veterans and first responders with chronic PTSD, MDMA doses of 75 mg and 125 mg combined with psychotherapy significantly reduced PTSD symptoms compared to a 30 mg dose, with large effect sizes indicating strong efficacy.

The treatment was well tolerated, with only 5% of reported adverse events being serious, suggesting that MDMA-assisted psychotherapy is a safe option for this population when administered in a controlled setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Mithoefer, MC., Mithoefer, AT., Feduccia, AA., et al.[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]

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-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]

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 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]

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 FDA and the Spanish Ministry of Health have approved pilot studies for MDMA-assisted psychotherapy in chronic PTSD patients who have not responded to conventional treatments, indicating a favorable risk/benefit ratio for this approach.

These studies, funded by the Multidisciplinary Association for Psychedelic Studies (MAPS), aim to rigorously evaluate the safety and efficacy of MDMA in treating PTSD over a five-year period, with an estimated cost of 5 million dollars.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical plan for MDMA (Ecstasy) in the treatment of posttraumatic stress disorder (PTSD): partnering with the FDA. Doblin, R.[2013]

Phase II trials have shown that MDMA-assisted psychotherapy is both safe and effective for treating posttraumatic stress disorder (PTSD), with potential applications for depression and anxiety disorders.

The unique approach of using MDMA in a psychotherapy setting, rather than daily drug administration alone, may allow for faster testing and approval through regulatory pathways like the FDA's Breakthrough Therapy Designation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Psychiatric Uses for MDMA. Yazar-Klosinski, BB., Mithoefer, MC.[2018]

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 study involving six couples where one partner had PTSD, MDMA-facilitated cognitive-behavioral conjoint therapy (CBCT) showed significant improvements in PTSD symptoms and relationship satisfaction, with effect sizes ranging from 1.85 to 3.59.

The treatment was safe and well-tolerated, with no serious adverse events reported, suggesting that MDMA can enhance the effectiveness of therapy for both individual and relational functioning in PTSD cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial. Monson, CM., Wagner, AC., Mithoefer, AT., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39955464/

MDMA-Assisted Therapy for Post-Traumatic Stress Disorder Early-phase clinical trials of MDMA-assisted therapy (MDMA-AT) showed promising results, leading the FDA to grant breakthrough therapy status to MDMA-AT in 2017 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06044675

MDMA-Assisted CBCT for PTSD vs CBCT RCT The effects of MDMA are reduced fear, enhanced communication, trust and introspection, and increased empathy and compassion. The effects of MDMA create a state ...

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2451865424000619

MDMA-assisted brief cognitive behavioral conjoint therapy ... Results showed large improvements in PTSD (d = 2.10), with 5 out of 6 patients showing sustained remission of PTSD diagnosis for 6 months. Other ...

5. icer.org icer.org/wp-content/uploads/2023/11/PTSD_Revised-Scope_For-Publication_11302023.pdf

MDMA-Assisted Therapy for Post-Traumatic Stress ... This project will evaluate the health and economic outcomes of MDMA-AT for PTSD. ... Expectancy Effects Cannot Be Neglected in MDMA-Assisted.

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

Midomafetamine-Assisted Psychotherapy for Post- ... 8 Commonly used psychotherapies include trauma-focused cogni ve-behavioral therapy (CBT), prolonged exposure. (PE) therapy, and eye movement ...