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.