MDMA-Assisted Therapy for PTSD

Recruiting at 1 trial location

Overseen By Stephen Marder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stephen Robert Marder

Must not be taking: Psychiatric medication

Disqualifiers: Significant disorders, Illegal drug abuse, 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

Compensation: Varies

Number of Visits: 11

Duration: 6 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two treatments for adults with moderate to severe PTSD. One treatment uses MDMA to help patients feel more comfortable during therapy, and the other uses a small dose of d-amphetamine to help them stay focused. The goal is to see if these treatments can reduce PTSD symptoms. MDMA has recently been shown as a novel therapeutic agent with promising results in the treatment of PTSD.

Will I have to stop taking my current medications?

The trial requires participants to safely taper off certain psychiatric medications. If you are taking any psychiatric drugs, you may need to stop them before joining the study.

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

Research shows that MDMA-assisted therapy significantly reduces PTSD symptoms compared to a placebo, with improvements in both symptom severity and daily functioning. This treatment has been found to be safe and well-tolerated, even in individuals with additional mental health challenges. ^{1 2 3 4 5}

Is MDMA-assisted therapy safe for humans?

MDMA-assisted therapy for PTSD has been found to be safe and well-tolerated in clinical trials, with no significant adverse events related to abuse potential, suicidality, or heart issues. However, it can increase blood pressure, heart rate, and body temperature, so it should be administered in controlled settings. ^{3 4 5 6 7}

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

MDMA-assisted therapy for PTSD is unique because it combines the drug MDMA with psychotherapy, which enhances the effectiveness of therapy sessions. Unlike standard treatments, this approach has shown significant improvements in PTSD symptoms, even in patients who have not responded to other treatments, and is considered safe and well-tolerated. ^{1 2 4 8 9}

Research Team

Stephen Marder, MD

Principal Investigator

VA Greater Los Angeles Healthcare System

Stephanie L Taylor, PhD

Principal Investigator

VA Greater Los Angeles Healthcare System

Eligibility Criteria

This trial is for veterans in the Greater Los Angeles area who have moderate to severe PTSD. Participants must be fluent in English, able to use effective contraception if applicable, and willing to have therapy sessions recorded. They should not be abusing drugs or involved in other clinical studies.

Inclusion Criteria

A person able to be pregnant (PABP) must use a highly effective contraceptive method

At Screening, meet DSM-5 criteria for current PTSD with a symptom duration of at least 6 months

My high blood pressure is well-managed with medication.

Exclusion Criteria

Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research, unless approved by the study clinician

Have evidence or history of significant medical or psychiatric disorders

Are abusing illegal drugs

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phone screen, 1 in-person visit

Preparatory

Medication tapering, three preparatory sessions, baseline assessments

4 weeks

3 visits (in-person)

Treatment

Three experimental sessions with MDMA or d-amphetamine, followed by integrative sessions

6 weeks

6 visits (in-person)

Follow-up

Primary outcome CAPS-5 assessment and study termination visit

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• 3,4-methylenedioxymethamphetamine
• d-amphetamine

Trial Overview The study compares MDMA-assisted therapy with low dose d-amphetamine-assisted therapy for PTSD symptoms. It's a phase II trial where participants are randomly assigned to one of the two treatments without knowing which one they're receiving.

Participant Groups

Group I: MDMA-Assisted Therapy Experimental Treatment 2 Interventions

Participants will receive a flexible divided-dose of MDMA plus therapy at Experimental Sessions.

Group II: Low Dose D-Amphetamine Assisted Therapy Active Control 2 Interventions

Participants will receive a flexible divided dose plus therapy at Experimental Sessions.

Who Is Running the Clinical Trial?

Stephen Robert Marder

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

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 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 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]

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]

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]

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]

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]

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 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]

References

1. 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]

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

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

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

MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study. [2023]

5. 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]

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

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

7. Ireland pubmed.ncbi.nlm.nih.gov

In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. [2021]

8. 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]

9. 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]