MDMA for Schizophrenia

(TMS Trial)

Overseen By Gerard De Vera

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Anya Bershad, MD, PhD

Must be taking: Antipsychotics

Must not be taking: SSRIs, SNRIs, Benzodiazepines

Disqualifiers: Neurological disease, Cardiovascular condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 6

Duration: 3 sessions

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether MDMA, a substance known for increasing social feelings, can aid people with schizophrenia who struggle with social motivation. Researchers aim to determine if MDMA is safe and well-tolerated in these patients, examining changes in symptoms like disorganized speech or hallucinations after taking the drug. Participants will try different doses of MDMA to identify the optimal amount that is both safe and effective. The study seeks individuals who have been stable with their schizophrenia for at least six months, without recent medication changes or hospitalizations. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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

The trial requires that you have not changed your medications for six months before joining, and you cannot be taking SSRIs or SNRIs. Additionally, you must not take sedatives or benzodiazepines within 24 hours of testing.

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

Research has shown that MDMA might help with certain mental health conditions and could improve social motivation in people with schizophrenia. However, safety remains a major concern. Studies have found that about 20% of recreational MDMA users experience mental health issues. Long-term use can lead to serious problems like psychosis, where individuals lose touch with reality.

This clinical trial tests MDMA's safety for people with schizophrenia by administering gradually increasing doses and monitoring for any rise in psychotic symptoms. As an early-stage trial, researchers are still determining MDMA's safety for this group. While MDMA might assist with social challenges in schizophrenia, further research is needed to ensure its safety. ^{1 2 3 4 5}

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

Researchers are excited about using MDMA for schizophrenia because it introduces a completely different approach compared to traditional treatments. Most treatments for schizophrenia focus on balancing neurotransmitters like dopamine with antipsychotic medications. However, MDMA, commonly known for its use in therapy for PTSD, has a unique mechanism that enhances emotional connectivity and empathy, which could offer new insights into managing symptoms. This distinct action could potentially help patients process emotions and experiences more effectively, offering a hopeful alternative to those who don't respond well to existing medications.

What evidence suggests that MDMA might be an effective treatment for schizophrenia?

Research has shown that MDMA, also known as ecstasy, might help with social challenges in people with schizophrenia. MDMA boosts feelings of empathy and social connection by affecting brain chemicals like oxytocin and serotonin, which are linked to social bonding and mood. While MDMA is primarily recognized for aiding PTSD, its positive effects on social behavior suggest it might also benefit those with schizophrenia who struggle with social motivation. Although specific studies on schizophrenia remain limited, the drug's success in other conditions offers hope. Participants in this trial will receive MDMA in ascending doses to evaluate its effects on social challenges in schizophrenia. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with a clinical diagnosis of schizophrenia, who have been stable for at least six months without hospitalizations or medication changes. Participants must understand English well enough to follow testing procedures.

Inclusion Criteria

I have been diagnosed with schizophrenia.

able to understand spoken English sufficiently to comprehend testing procedures

I haven't been hospitalized or changed my medication in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ascending doses of MDMA (40mg, 80mg, 120mg) to assess tolerability

3 sessions

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after each treatment session

24 hours after each session

3 follow-up assessments (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• MDMA

Trial Overview The study explores the use of MDMA to improve social motivation in schizophrenia patients. It's an open-label trial where participants will take increasing doses of MDMA (40mg, then 80mg, and potentially up to 120mg) while monitoring their tolerance and psychotic symptoms after each dose.

How Is the Trial Designed?

Group I: MDMA Experimental Treatment 3 Interventions

Each subject will receive 3 doses of MDMA in ascending order: 40mg, 80mg, 120mg.

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?

Anya Bershad, MD, PhD

Lead Sponsor

Trials

1

Recruited

20+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

MDMA, commonly known as ecstasy, is often mistakenly believed to be a safe drug, but its use has led to significant health risks, including serious cardiovascular effects and long-term neuropsychiatric issues.

The review highlights the increasing prevalence of ecstasy use among teenagers and young adults, emphasizing the need for awareness of its potential for toxicity and the importance of proper emergency care for those affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ecstasy toxicity]. Reingardiene, D.[2018]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9225098/

MDMA for the Treatment of Negative Symptoms in ... MDMA, with its inherent oxytocinergic and serotonergic effects, is poised for therapeutic benefit in negative symptoms. To date, no lab studies ...

2. uclahealth.org uclahealth.org/clinical-trials/tolerability-mdma-schizophrenia

Tolerability of MDMA in Schizophrenia One promising and unexplored avenue to enhance social motivation in schizophrenia is ± 3,4-methylenedioxymethamphetamine (MDMA). MDMA is a psychostimulant ...

3. reporter.nih.gov reporter.nih.gov/project-details/10932872

MDMA as a Treatment for Social Deficits in Schizophrenia MDMA has shown promise in other psychiatric conditions such as PTSD. Thus, MDMA could offer a unique therapeutic benefit in patients with schizophrenia who ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05770375

NCT05770375 | Tolerability of MDMA in Schizophrenia One promising and unexplored avenue to enhance social motivation in schizophrenia is ± 3,4-methylenedioxymethamphetamine (MDMA).

5. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20230681

MDMA and MDMA-Assisted Therapy | American Journal of ... A considerable body of preliminary evidence suggests that MDMA-AT delivered in a controlled clinical setting is a safe and efficacious treatment for PTSD.

6. cureus.com cureus.com/articles/243382-navigating-treatment-challenges-a-case-study-on-refractory-psychosis-in-a-chronic-mdma-34-methylenedioxymethamphetamine-user

A Case Study on Refractory Psychosis in a Chronic MDMA ... Despite its deceptive reputation as "safe," chronic MDMA use is associated with neuropsychiatric complications, including psychosis. We describe ...

7. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20230681

MDMA and MDMA-Assisted Therapy | American Journal of ... In a review of 199 case reports of nonclinical Ecstasy use, approximately 20% reported psychiatric concerns (91).

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38832158/

A Case Study on Refractory Psychosis in a Chronic MDMA ... Despite its deceptive reputation as "safe," chronic MDMA use is associated with neuropsychiatric complications, including psychosis. We describe ...