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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combining MDMA (a psychoactive drug) with therapy to assist military veterans dealing with both PTSD and alcohol use disorder. The goal is to determine if this approach can reduce alcohol use and improve PTSD symptoms. The trial includes therapy sessions with MDMA doses and additional non-drug therapy sessions. Veterans diagnosed with PTSD for at least six months and who struggle with alcohol use may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that MDMA-assisted therapy (MDMA-AT) is generally well-tolerated by people with PTSD. One study found that MDMA-AT helped reduce PTSD symptoms and was safe for participants. Another study examined the safety of MDMA-AT and concluded it could be used safely for those with long-term, hard-to-treat PTSD. While side effects can occur, these studies suggest that the treatment is generally well-tolerated. Prospective participants should discuss potential risks with the study team. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for PTSD and Alcoholism?

MDMA is unique because it combines the effects of a psychedelic compound with assisted therapy to treat PTSD and alcoholism. Unlike traditional treatments like SSRIs or cognitive behavioral therapy, MDMA acts on serotonin receptors, potentially enhancing emotional processing and empathy during therapy sessions. Researchers are excited about its potential to produce rapid and long-lasting improvements, possibly offering relief within just a few therapy sessions, compared to weeks or months with standard treatments.

What evidence suggests that MDMA might be an effective treatment for PTSD and Alcoholism?

Research shows that MDMA-assisted therapy (MDMA-AT), which participants in this trial will receive, holds promise for reducing PTSD symptoms. Studies indicate it can help people who haven't benefited from other treatments by increasing brain chemicals like serotonin and oxytocin. The FDA has labeled MDMA-AT as a Breakthrough Therapy for PTSD due to strong safety and effectiveness data from past studies. Although less information exists on its impact on alcohol use disorder (AUD), this trial aims to treat both conditions together, introducing a new approach. Overall, evidence supports MDMA-AT as effective in easing PTSD symptoms. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

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

I have high blood pressure.

I have had seizures or delirium tremens.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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, 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, 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 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 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]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10660711/

MDMA-Based Psychotherapy in Treatment-Resistant Post ... MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, ie, dopamine, serotonin, norepinephrine, and oxytocin.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6435835/

A Review of 3,4-methylenedioxymethamphetamine (MDMA) Most clinical MDMA research in patients to date has focused on MDMA-assisted psychotherapy to treat posttraumatic stress disorder (PTSD). In this review paper ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2451865424000802

Design and methodology of the first open-label trial ... In 2017, the FDA designated MDMA-AT as a Breakthrough Therapy for PTSD based on promising safety and efficacy results from six completed Phase 2 clinical trials ...

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

Midomafetamine-Assisted Psychotherapy for Post- ... The Efficacy of MDMA (3,4-. Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3122379/

the first randomized controlled pilot study The hypothesis tested is that MDMA could be administered without harm to people with chronic, treatment-resistant PTSD and, in conjunction with psychotherapy, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178124003287

The efficacy and safety of MDMA-assisted psychotherapy ... This study aimed to systematically review and demonstrate the efficacy and safety of MDMA-assisted psychotherapy for the treatment of PTSD.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06989957?cond=Post%20Traumatic%20Stress%20Disorder&intr=%22Psilocybin%22&viewType=Table&rank=3

Study Details | NCT06989957 | Psilocybin and ... The purpose of this study is to assess the safety and effectiveness of co-administered MDMA and psilocybin in military Veterans with a diagnosis of ...