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

Trial Summary

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 MDMA generally safe for humans?

MDMA, also known as Ecstasy, has been linked to serious health issues, including psychological disorders and neurotoxic effects. It can cause severe reactions like serotonin syndrome and neuroleptic malignant syndrome, and its use has been associated with lasting adverse effects, especially in high doses. ^{1 2 3 4 5}

How is the drug MDMA different from other treatments for schizophrenia?

MDMA is unique because it is primarily known as a recreational drug and has been studied for its potential in treating posttraumatic stress disorder, but its use for schizophrenia is novel and not well-documented. Unlike traditional antipsychotic medications, MDMA's effects on schizophrenia are not well understood, and it has been associated with psychiatric symptoms and potential toxicity. ^{5 6 7 8 9}

What is the purpose of this trial?

Impaired social motivation, or "asociality," is a negative symptom of schizophrenia (SCZ) and a cause of significant functional impairment in the illness. Whereas many symptoms of schizophrenia can be treated with antipsychotic medications, deficits in social motivation persist, leading to significant social disability in patients. There is currently no effective treatment for this symptom of the illness. One promising and unexplored avenue to enhance social motivation in schizophrenia is ± 3,4-methylenedioxymethamphetamine (MDMA). MDMA is a psychostimulant that shares some pharmacological properties with amphetamines, but in addition, has pronounced pro-social effects, increasing the motivation to engage socially. In healthy volunteers, it produces feelings of empathy and closeness with others and increases attention to positive social cues, perhaps partly through its effects on the social bonding hormone, oxytocin. MDMA has shown promise in other psychiatric conditions such as PTSD. Thus, MDMA could offer a unique therapeutic benefit in patients with SCZ who suffer from impaired social motivation. The investigators plan to take the first step in testing MDMA as a treatment for these social deficits by testing the tolerability of the drug in patients with SCZ. This will be an open-label, ascending-dose, within-subject trial in which participants will receive 40mg, 80mg, or 120mg of MDMA. The doses will be administered in ascending order, but doses will be stopped if subjects experience moderate or greater psychotic symptoms at 24 hours. This trial will assess the tolerability of the drug in this population and guide in the selection of a maximum well-tolerated dose for future studies. The primary tolerability measure will be clinician-rated psychotic symptoms (disorganized speech, delusions, hallucinations) collected at 24 hours after MDMA administration. The results of this project will lay the foundation for further investigations of MDMA and other psychoactive compounds as a treatment for debilitating and difficult-to-treat social deficits in schizophrenia. Future studies will examine interactions between the effects of psychoactive compounds and nonpharmacologic psychosocial interventions targeting social symptoms.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Ecstasy intoxication: an overlap between serotonin syndrome and neuroleptic malignant syndrome. [2019]

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

Lasting neuropsychiatric sequelae of (+-)methylenedioxymethamphetamine ('ecstasy') in recreational users. [2013]

3. Switzerland pubmed.ncbi.nlm.nih.gov

[Ecstasy toxicity]. [2018]

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

Toxicity of MDA (3,4-methylenedioxyamphetamine) considered for relevance to hazards of MDMA (Ecstasy) abuse. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Estonia pubmed.ncbi.nlm.nih.gov

Expression of bax and bcl2 Genes in MDMA-induced Hepatotoxicity on Rat Liver Using Quantitative Real-Time PCR Method through Triggering Programmed Cell Death. [2020]

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

'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Prevalence and Correlates of Past Year Ecstasy/MDMA Use in the United States. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Diversity of psychopathology associated with use of 3,4-methylenedioxymethamphetamine ('Ecstasy') [2019]