Tolerability of MDMA in Schizophrenia (TMS)

Anya Bershad, MD, PhD

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Schizophrenia

Treatments

Drug: MDMA 80mg

Drug: MDMA 120mg

Drug: MDMA 40mg

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT05770375

IRB#22-001600

1DP5OD036172-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment

20 estimated patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

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