The profound economic burden of schizophrenia is due, in part, to the negative symptoms of the disease, which can severely limit daily functioning. There is much debate in the field regarding their measurement and classification and there are no FDA-approved treatments for negative symptoms despite an abundance of research. 3,4-Methylenedioxy methamphetamine (MDMA) is a schedule I substance that has emerged as a novel therapeutic given its ability to enhance social interactions, generate empathy, and induce a state of metaplasticity in the brain. This review provides a rationale for the use of MDMA in the treatment of negative symptoms by reviewing the literature on negative symptoms, their treatment, MDMA, and MDMA-assisted therapy. It reviews recent evidence that supports the safe and potentially effective use of MDMA to treat negative symptoms and concludes with considerations regarding safety and possible mechanisms of action.
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