Abstract
The use of (±)-3,4-methylenedioxymethamphetamine ((±)-MDMA) as an adjunct to psychotherapy in the treatment of psychiatric and behavioral disorders dates back over 50 years. Only in recent years have controlled and peer-reviewed preclinical and clinical studies lent support to (±)-MDMA’s hypothesized clinical utility. However, the clinical utility of (±)-MDMA is potentially mitigated by a range of demonstrated adverse effects. One potential solution could lie in the individual S(+) and R(−) enantiomers that comprise (±)-MDMA. Individual enantiomers of racemic compounds have been employed in psychiatry to improve a drug’s therapeutic index. Although no research has explored the individual effects of either S(+)-MDMA or R(−)-MDMA in humans in a controlled manner, preclinical research has examined similarities and differences between the two molecules and the racemic compound. This review addresses information related to the pharmacodynamics, neurotoxicity, physiological effects, and behavioral effects of S(+)-MDMA and R(−)-MDMA that might guide preclinical and clinical research. The current preclinical evidence suggests that R(−)-MDMA may provide an improved therapeutic index, maintaining the therapeutic effects of (±)-MDMA with a reduced side effect profile, and that future investigations should investigate the therapeutic potential of R(−)-MDMA.
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M.B.Y. became employed by Shire Pharmaceuticals (Lexington, MA, USA) after completion of the studies described herein. M.B.Y. was supported by a NIH/NIGMS IRACDA grant K21 GM000680 awarded to Emory University. L.L.H. was supported by NIH/NIDA K05 DA031246. The Yerkes National Primate Research Center is supported by NIH P51OD11132. The other authors declare that they have no conflicts of interest.
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Pitts, E.G., Curry, D.W., Hampshire, K.N. et al. (±)-MDMA and its enantiomers: potential therapeutic advantages of R(−)-MDMA. Psychopharmacology 235, 377–392 (2018). https://doi.org/10.1007/s00213-017-4812-5
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DOI: https://doi.org/10.1007/s00213-017-4812-5