(R)-3,4-Methylenedioxy-N-methylamphetamine ((R)-MDMA), also known as (R)-midomafetamine or as levo-MDMA, is the (R)- or levorotatory (l-) enantiomer of 3,4-methylenedioxy-N-methylamphetamine (MDMA; midomafetamine; "ecstasy"), a racemic mixture of (R)-MDMA and (S)-MDMA.

[3][5] In clinical studies, (R)-MDMA produces similar effects to MDMA and (S)-MDMA, but is less potent and has a longer duration.

[7][8][9] It is thought that (R)-MDMA might have a better safety profile than MDMA itself whilst retaining its therapeutic benefits.

[2][5] In addition to its actions as an SNDRA, MDMA has weak affinity for the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, where it acts as an agonist.

[3][5] As (R)-MDMA is less neurotoxic than (S)-MDMA and MDMA or even non-neurotoxic, it may allow for greater clinical viability and prolonged regimens of drug-assisted psychotherapy.

[3][5] MDMA and (S)-MDMA increase locomotor activity, a measure of psychostimulant-like effect, in rodents, whereas (R)-MDMA does not do so.

[3] These findings further add to (R)-MDMA showing reduced psychostimulant-like and addictive effects compared to MDMA and (S)-MDMA.

[3] The first modern clinical study of the comparative effects of MDMA, (R)-MDMA, and (S)-MDMA was published in August 2024.

[2] However, (S)-MDMA 125 mg was more potent in increasing subjective effects, including stimulation, drug high, happy, and open, among others, than (R)-MDMA 125 or 250 mg or MDMA 125 mg.[1][2] Ratings of bad drug effect and fear were minimal with MDMA, (R)-MDMA, and (S)-MDMA.

[1][2] It was estimated that equivalent effects would be expected with (S)-MDMA 100 mg, MDMA 125 mg, and (R)-MDMA 300 mg.[1][2] The findings of the study were overall regarded as not supporting the hypothesis that (R)-MDMA would produce equivalent therapeutic effects as (S)-MDMA or MDMA whilst reducing safety concerns.

[1][2] However, more clinical studies were called for to assess the revised estimated equivalent doses of MDMA, (R)-MDMA, and (S)-MDMA.