Tolerability of MDMA in Schizophrenia

NCT ID: NCT05770375

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2027-03-31

Brief Summary

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MDMA

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

Group Type: EXPERIMENTAL

MDMA 40mg

Intervention Type: DRUG

MDMA 40mg

MDMA 80mg

Intervention Type: DRUG

MDMA 80mg

MDMA 120mg

Intervention Type: DRUG

MDMA 120mg

Interventions

MDMA 40mg

MDMA 40mg

Intervention Type: DRUG

MDMA 80mg

MDMA 80mg

Intervention Type: DRUG

MDMA 120mg

MDMA 120mg

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ages 18-60
• able to understand spoken English sufficiently to comprehend testing procedures
• DSM-5 diagnosis of schizophrenia, based on clinical interview
• clinical stability (i.e., no inpatient hospitalizations for six months prior to enrollment, no changes in medication in for 6 months prior to enrollment)

Exclusion Criteria

• no history of aggressive or suicidal behavior while psychotic
• no history of IQ less than 70 or developmental disability, based on medical history
• no clinically significant neurological disease (e.g., epilepsy), or cardiovascular condition (e.g. cardiac arrhythmia) based on medical history
• no history of serious head injury (i.e., loss of consciousness longer than 1 hour, neuropsychological sequelae, cognitive rehabilitation treatment after head injury) based on medical history
• no substance or alcohol use disorder in the past six months
• no sedatives or benzodiazepines within 24 hours of testing
• no positive urine toxicology screen or visible intoxication on the day of assessment
• no women who are pregnant or think that they might be pregnant, based on self-report and urine test
• not currently taking SSRIs or SNRIs
• no history of NMS or serotonin syndrome
• No prolongation of the QTc interval on EKG

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Anya Bershad, MD, PhD

OTHER

Sponsor Role: lead

Responsible Party

Anya Bershad, MD, PhD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

UCLA

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Gerard De Vera

Role: CONTACT

gdevera@mednet.ucla.edu

310-794-5577

Facility Contacts

Gerard De Vera

Role: primary

gdevera@mednet.ucla.edu

310-794-5577

Other Identifiers

1DP5OD036172-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB#22-001600

Identifier Type: -

Identifier Source: org_study_id