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

16 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this pilot trial is to examine the preliminary effectiveness of MDMA-facilitated bCBCT for improving chronic PTSD and relationship functioning in a sample of veterans and their intimate partners seeking care within the VA San Diego Healthcare System.

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.

What data supports the effectiveness of the drug MDMA-assisted therapy for PTSD?

Research shows that MDMA-assisted therapy can lead to significant improvements in PTSD symptoms, with one study reporting an 83% response rate in patients who received MDMA compared to 25% in those who did not. Additionally, combining MDMA with cognitive-behavioral conjoint therapy has shown improvements in PTSD symptoms and relationship satisfaction. ^{1 2 3 4 5}

Is MDMA-assisted therapy safe for humans?

Research shows that MDMA-assisted therapy can be safely administered in a clinical setting, with no serious drug-related adverse events reported in studies. Low doses of MDMA have been found to be both psychologically and physically safe for participants. ^{1 2 5 6 7}

How is MDMA-assisted therapy for PTSD different from other treatments?

MDMA-assisted therapy for PTSD is unique because it combines the drug MDMA with Cognitive Behavioral Conjoint Therapy (CBCT), which involves both the patient and their partner in therapy sessions. This approach not only aims to reduce PTSD symptoms but also improves relationship satisfaction, making it distinct from traditional individual therapies. ^{1 2 4 5 8}

Research Team

Leslie Morland

Principal Investigator

San Diego Veterans Healthcare System

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

References

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

Combining Cognitive-Behavioral Conjoint Therapy for PTSD with 3,4-Methylenedioxymethamphetamine (MDMA): A Case Example. [2020]

2. United States 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). [2013]

3. England 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. [2019]

4. 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]

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

MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial. [2021]

6. 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]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

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