MDMA-Assisted Therapy for PTSD

(MDMA-bCBCT Trial)

Overseen By Leslie A. Morland, PsyD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Dr. Leslie Morland

Must not be taking: Psychiatric medications

Disqualifiers: Psychotic disorder, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 7-13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether MDMA-assisted therapy can help veterans and their partners improve chronic PTSD symptoms and relationship issues. The treatment combines MDMA with Brief Cognitive Behavioral Conjoint Therapy (bCBCT). Veterans with PTSD and their partners committed to working on their relationship might be suitable candidates. Participants must engage in therapy and be open to medication sessions. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial requires participants to refrain from certain medications before MDMA sessions, but it doesn't specify which ones. It's best to discuss your current medications with the study physician to ensure they don't interfere with the trial.

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

Research has shown that MDMA-assisted therapy, combined with brief cognitive behavioral conjoint therapy (bCBCT), is generally safe. In past studies, participants did not report any serious side effects, and most handled the treatment well. Some mild side effects, such as anxiety or headaches, were noted but were uncommon. This suggests the treatment is well-tolerated.

MDMA is already used in some PTSD (post-traumatic stress disorder) treatments, offering reassurance about its safety. While more research is needed, current evidence indicates the treatment can be safe with careful supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Unlike the standard treatments for PTSD, which often include prolonged exposure therapy or medications like SSRIs, MDMA-assisted therapy combines psychotherapy with a unique active ingredient, MDMA. This approach is exciting because MDMA can enhance emotional openness and reduce fear, allowing patients to engage more deeply in therapy sessions. Researchers are hopeful that this combination could lead to quicker and more substantial relief from PTSD symptoms compared to traditional methods.

What evidence suggests that MDMA-assisted therapy is effective for PTSD?

Research shows that using MDMA in therapy, along with a short form of cognitive behavioral therapy for couples, may help treat PTSD (post-traumatic stress disorder). In this trial, participants will receive non-medicine sessions of brief Cognitive Behavioral Conjoint Therapy (bCBCT) combined with medicine sessions using MDMA. Early studies with couples, where one partner has PTSD, have shown significant improvements not only in PTSD symptoms but also in depression, sleep, and emotional well-being. Participants in these studies reported feeling better and having improved relationships, suggesting that this treatment can address both mental health and relationship issues. Additionally, using MDMA with therapy appears to enhance the treatment's effectiveness compared to therapy alone. These findings offer hope that MDMA-assisted therapy could effectively treat PTSD. ^{1 2 3 4 5}

Who Is on the Research Team?

Leslie Morland

Principal Investigator

San Diego Veterans Healthcare System

Are You a Good Fit for This Trial?

This trial is for veterans with PTSD and their partners who've been together for at least a year. Participants must speak English, commit to the study schedule, not start new mental health care during the trial, and agree to lifestyle changes. Women able to get pregnant must use birth control. Exclusions include severe relationship aggression, high risk of re-trauma or lack of support, certain psychiatric conditions or substance abuse issues.

Inclusion Criteria

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

I agree to fast and stop certain medications before MDMA sessions.

Exclusion Criteria

I am a veteran with PTSD and have had ECT in the last 12 weeks.

Are likely, in the investigator's opinion and via assessment period, to be re-exposed to their index trauma or other significant trauma, lack social support, or lack a stable living situation

Have a history of or a current Bipolar I disorder, Bipolar 2 disorder, or manic episode assessed via the DIAMOND and clinical interview (PTSD+ veteran only)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

12 weeks

Treatment

Participants receive MDMA-assisted therapy combined with brief Cognitive Behavioral Conjoint Therapy over 8 sessions, including two full-day MDMA sessions.

7-13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MDMA-assisted Brief Cognitive Behavioral Conjoint Therapy

Trial Overview The study tests if MDMA can help improve PTSD symptoms and relationship functioning when combined with brief cognitive behavioral conjoint therapy (bCBCT). Veterans with PTSD and their partners will undergo this combination treatment within the VA San Diego Healthcare System.

How Is the Trial Designed?

Group I: Non-medicine sessions of bCBCT + Medicine Sessions with 3,4-methylenedioxymethamphetamine (MDMA) Experimental Treatment 2 Interventions

bCBCT Non-medicine sessions: 8 sessions MDMA Medicine sessions: Initial Dose 1: 80 mg MDMA HCl (\~68 mg MDMA) Supplementary Dose 1: 40 mg MDMA HCl (\~34 mg MDMA) Initial Dose 2: 100 mg MDMA HCl (\~84 mg MDMA) Supplementary Dose 2: 40 mg MDMA HCl (\~34 mg MDMA)

Who Is Running the Clinical Trial?

Dr. Leslie Morland

Lead Sponsor

Trials

1

Recruited

20+

MAPS Public Benefit Corporation

Industry Sponsor

Trials

30

Recruited

900+

MAPS Public Benefit Corporation

Collaborator

Trials

2

Recruited

30+

Healing Breakthrough

Collaborator

Trials

2

Recruited

30+

Lykos Therapeutics

Industry Sponsor

Trials

32

Recruited

960+

San Diego Veterans Healthcare System

Collaborator

Trials

38

Recruited

5,500+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

Cognitive Behavioral Conjoint Therapy (CBCT) combined with MDMA-assisted psychotherapy shows promise in reducing PTSD symptoms and improving relationship satisfaction, as demonstrated in a pilot trial with a representative couple.

Historically, PTSD treatments have evolved to include various evidence-based options, with cognitive behavioral therapies achieving significant symptom improvement in 50-60% of patients, highlighting the potential benefits of integrating new approaches like MDMA with established therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Cognitive-Behavioral Conjoint Therapy for PTSD with 3,4-Methylenedioxymethamphetamine (MDMA): A Case Example. Wagner, AC., Mithoefer, MC., Mithoefer, AT., et al.[2020]

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]

Citations

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

MDMA-assisted brief cognitive behavioral conjoint therapy ... This is a single site, open-label study assessing the preliminary efficacy, safety, and acceptability of MDMA-assisted therapy in combination with bCBCT in 8 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38994348/

MDMA-assisted brief cognitive behavioral conjoint therapy ... This is the first study to examine the efficacy of MDMA-assisted bCBCT for improving PTSD and relationship functioning among a sample of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06044675

MDMA-Assisted CBCT for PTSD vs CBCT RCT This study aims to evaluate the safety, feasibility, acceptability, and effectiveness of MDMA-assisted Cognitive-Behavioral Conjoint Therapy (CBCT) versus ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7748057/

MDMA-facilitated cognitive-behavioural conjoint therapy for ... MDMA was combined with cognitive-behavioural conjoint therapy for PTSD in six couples revealing significant improvements in PTSD, depression, sleep, emotion ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02876172

Study Details | NCT02876172 | MDMA-Assisted Cognitive- ... The goal of this clinical trial is to learn if cognitive-behavioral conjoint therapy (CBCT) in combination with MDMA-assisted therapy is safe and effective ...