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Peer-reviewed article

<i>R</i>-MDDMA is a Safer Analogue of MDMA with Therapeutic Potential.

Vargas MV, Hatzipantelis CJiD, Dunlap LE, Tombari RJiD, Avanes AA, Vaillancourt SiD, Llorach P, Salgado JS, Heifets BDiD, Olson DEiD

ACS chemical neuroscienceApr 20, 2026United States0 citationsDOI: 10.1021/acschemneuro.5c00891

Abstract

Recent clinical evidence suggests that racemic 3,4-methylenedioxymethamphetamine (MDMA) might be useful for treating a range of neuropsychiatric diseases including post-traumatic stress disorder (PTSD) and depression. However, concerns about its abuse potential stemming from its monoamine releasing properties have hampered its clinical development. Thus, safer analogues of racemic MDMA with comparable therapeutic effects are highly desirable. Here, we compare the pharmacological effects of MDMA enantiomers with those of its methylated analogue 3,4-methylenedioxy-<i>N</i>,<i>N</i>-dimethylamphetamine (MDDMA). We found that <i>R</i>-MDDMA did not directly activate 5-HT2B receptors, induce serotonin efflux, produce a head-twitch response, impact body temperature, or induce hyperlocomotion at therapeutically relevant doses. However, it still promoted structural neuroplasticity in cortical neurons, facilitated fear extinction learning, and produced sustained antidepressant-like effects. Taken together, our results suggest that <i>R</i>-MDDMA might be a safer MDMA analogue with similar therapeutic properties.

Topics & conditions

Detected automatically by Psychedelic Commons from the title and abstract, not labels from the source. They may be incomplete.

MDMADepressionPTSD

Keywords

EntactogenPsychedelicPsychoplastogenMddma

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