MDMA for PTSD and Alcoholism

(MDMA Trial)

Overseen By Erica Eaton, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Carolina L Haass-Koffler

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: Liver disease, Hypertension, Arrhythmia, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The study investigators are conducting the first open label pilot trial of MDMA-assisted therapy (MDMA-AT) with a comorbid sample of military veterans with a comorbid diagnosis of Alcohol Use Disorder (AUD) and Post-Traumatic Stress Disorder (PTSD). This novel experimental treatment package consists of two once-monthly Experimental Sessions of therapy combined with a divided-dose of MDMA HCl, along with non-drug preparatory and integrative therapy. The Primary Outcome measure, the Timeline Follow-back (TLFB), will evaluate changes in alcohol use over time. Changes in PTSD symptoms will also be evaluated.

Will I have to stop taking my current medications?

The trial requires participants to taper off antidepressant medications before starting the study. If you are on SSRIs, you need approval from a physician to taper off. Other psychiatric medications and certain medications that prolong the QT interval are also not allowed during the study.

What data supports the effectiveness of the drug MDMA for PTSD and Alcoholism?

Research shows that MDMA-assisted therapy significantly reduces PTSD symptoms compared to a placebo, and it is safe and well-tolerated even in people with alcohol and substance use disorders. ^{1 2 3 4 5}

Is MDMA safe for use in humans?

MDMA has been studied for its use in treating PTSD, but it can increase blood pressure, heart rate, and body temperature. There is a risk of serotonin syndrome, especially when combined with other drugs, but no cases have been reported in clinical trials where MDMA was the only drug taken. Other potential risks include liver damage and cardiovascular events. ^{6 7 8 9 10}

How is the drug MDMA unique in treating PTSD and alcoholism?

MDMA is unique because it is used as a catalyst in psychotherapy, helping to treat PTSD by affecting brain regions like the amygdala and hippocampus, which are involved in emotional processing. Unlike traditional treatments, MDMA-assisted therapy has shown promise in treatment-resistant cases by enhancing the therapeutic process. ^{3 4 6 11 12}

Eligibility Criteria

This trial is for military veterans who have both Alcohol Use Disorder (AUD) and Post-Traumatic Stress Disorder (PTSD). Participants must be fluent in English, able to prove veteran status, meet specific criteria for AUD and PTSD with a certain severity of symptoms, can abstain from alcohol safely for 48 hours without medical detox, are capable of swallowing pills, and agree to recorded study visits. They also need a contact person available for emergencies.

Inclusion Criteria

I have agreed with my care team on a plan to manage my symptoms without self-medicating.

I have been diagnosed with PTSD and my severity score is 28 or higher.

I have Hepatitis C but it doesn't cause symptoms and I've been treated for it.

Exclusion Criteria

Current Personality Disorders assessed via the SCID-5-PD

Lack of social support or stable living situation

Sensitivity to any of the study interventions or components thereof

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Therapy

Participants engage in non-drug preparatory therapy sessions

4 weeks

Treatment

Participants receive two once-monthly Experimental Sessions of MDMA-assisted therapy

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments and optional imaging

6 weeks

Treatment Details

Interventions

• MDMA

Trial Overview The trial is testing MDMA-assisted therapy as a new treatment approach for veterans with AUD/PTSD comorbidity. It involves two monthly sessions where therapy is combined with divided doses of MDMA HCl. The main focus is on changes in alcohol use over time and improvements in PTSD symptoms.

Participant Groups

Group I: MDMA-AT Experimental Treatment 1 Intervention

Participant will receive MDMA administration with assisted therapy (AT) by trained clinicians

MDMA is already approved in United States for the following indications:

Approved in United States as MDMA for:

• Posttraumatic stress disorder (PTSD)

Who Is Running the Clinical Trial?

Carolina L Haass-Koffler

Lead Sponsor

Trials

1

Recruited

20+

Carolina Haass-Koffler

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

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 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]

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, once used as a therapeutic aid before being classified as a Schedule I drug in 1985, has shown promise in treating posttraumatic stress disorder (PTSD) when used in psychotherapy, despite limited research due to its scheduling.

The review highlights the brain regions affected by both PTSD and MDMA, such as the amygdala and hippocampus, suggesting that MDMA may work through specific neurochemical mechanisms to enhance therapeutic outcomes in PTSD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Psychopharmacology of ±3,4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder. Amoroso, T.[2015]

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]

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]

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 is being studied as a potential treatment for post-traumatic stress disorder (PTSD) and anxiety-related conditions, with promising results leading to expected FDA approval in the near future.

In a review of adverse events, no cases of serotonin syndrome (SS) were reported in clinical trials where MDMA was the only substance taken, suggesting that MDMA may be safe when used alone, although caution is warranted when combined with other serotonergic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. Makunts, T., Jerome, L., Abagyan, R., et al.[2022]

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]

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]

A review of psychiatric case studies over the last 10 years indicates a strong causal relationship between MDMA use and the onset of neuropsychiatric symptoms, with 76% of patients lacking a personal psychiatric history, suggesting that MDMA may trigger these issues in previously healthy individuals.

Ecstasy users, even those without clinical symptoms, show significantly higher psychological distress compared to those who have never used the drug, particularly among heavier users, highlighting the potential long-term mental health risks associated with MDMA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric disorders in Ecstasy (MDMA) users: a literature review focusing on personal predisposition and drug history. Soar, K., Turner, JJ., Parrott, AC.[2019]

References

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

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

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

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. [2023]

3. 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]

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

The Psychopharmacology of ±3,4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder. [2015]

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Prevalence and Correlates of Past Year Ecstasy/MDMA Use in the United States. [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. Switzerland pubmed.ncbi.nlm.nih.gov

Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. [2022]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

How MDMA's pharmacology and pharmacokinetics drive desired effects and harms. [2019]

11. Germany pubmed.ncbi.nlm.nih.gov

MDMA does not alter responses to the Trier Social Stress Test in humans. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Psychiatric disorders in Ecstasy (MDMA) users: a literature review focusing on personal predisposition and drug history. [2019]