Buy levo-MDMA Cas 81262-70-6

Buy levo-MDMA Cas 81262-70-6

(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][2] Like MDMA, (R)-MDMA is an entactogen or empathogen.^[3][2] It is taken by mouth.^[3][2]

The drug is a serotonin–norepinephrine releasing agent (SNRA) and weak serotonin 5-HT_2A receptor agonist.^[3][4] It has substantially less or no significant dopamine-releasing activity compared to MDMA and (S)-MDMA.^[3][4] In preclinial studies, (R)-MDMA shows equivalent therapeutic-like effects to MDMA, such as increased prosocial behavior, but shows reduced psychostimulant-like effects, addictive potential, and serotonergic neurotoxicity.^[3][5] In clinical studies, (R)-MDMA produces similar effects to MDMA and (S)-MDMA, but is less potent and has a longer duration.^[1][2]

(R)-MDMA was first described in enantiopure form by 1978.^[6] Under the developmental code names EMP-01, developed by atai Life Sciences,^[7] and MM-402, developed by MindMed,^[8] it is under development for the treatment of post-traumatic stress disorder (PTSD), social phobia, and pervasive development disorders (PDDs) such as autism.^[9][10][11] It is thought that (R)-MDMA might have a better safety profile than MDMA itself whilst retaining its therapeutic benefits.^[3]

(R)-MDMA has a dose of 125 to 300 mg orally and a duration of 3.5 to 5.2 hours.^[2] It has been estimated that doses of 125 mg MDMA, 100 mg (S)-MDMA, and 300 mg (R)-MDMA are equivalent.^[2]

The first modern clinical study of the comparative effects of MDMA, (R)-MDMA, and (S)-MDMA was published in August 2024.^[1][2] It compared 125 mg MDMA, 125 mg (S)-MDMA, 125 and 250 mg (R)-MDMA, and placebo.^[1][2] (R)-MDMA increased any drug effect, good drug effect, drug liking, stimulation, drug high, alteration of vision, and alteration of sense of time ratings similarly to MDMA and (S)-MDMA.^[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.^[2] In contrast to expectations, (R)-MDMA did not produce more psychedelic-like effects than (S)-MDMA.^[1][2] Besides subjective effects, (R)-MDMA increased heart rate, blood pressure, and body temperature similarly to MDMA and (S)-MDMA, though it was less potent in producing these effects.^[2] Body temperature was notably increased to the same extent with (R)-MDMA 250 mg as with MDMA 125 mg and (S)-MDMA 125 mg.^[2]

The differences in effects between (R)-MDMA and (S)-MDMA may reflect the higher potency of (S)-MDMA rather than actual qualitative differences between the effects of (S)-MDMA and (R)-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.^[1][2]

Activities of MDMA, its enantiomers, and related compounds

Compound	Monoamine release (EC50Tooltip half-maximal effective concentration, nM)
	Serotonin	Norepinephrine	Dopamine
Amphetamine	ND	ND	ND
(S)-Amphetamine (d)	698–1,765	6.6–7.2	5.8–24.8
(R)-Amphetamine (l)	ND	9.5	27.7
Methamphetamine	ND	ND	ND
(S)-Methamphetamine (d)	736–1,292	12.3–13.8	8.5–24.5
(R)-Methamphetamine (l)	4,640	28.5	416
MDA	160	108	190
(S)-MDA (d)	100	50	98
(R)-MDA (l)	310	290	900
MDMA	49.6–72	54.1–110	51.2–278
(S)-MDMA (d)	74	136	142
(R)-MDMA (l)	340	560	3,700
MDEA	47	2,608	622
(S)-MDEA (d)	465	RI	RI
(R)-MDEA (l)	52	651	507
MBDB	540	3,300	>100,000
MDAI	114	117	1,334
Notes: The smaller the value, the more strongly the compound produces the effect. Refs: [4][12][13][14][15][16][17][18]

MDMA is a well-balanced serotonin–norepinephrine–dopamine releasing agent (SNDRA).^[19][4][12] (R)-MDMA and (S)-MDMA are both SNDRAs similarly.^[19][4][12] However, (R)-MDMA is several-fold less potent than (S)-MDMA in vitro and is also less potent than (S)-MDMA in vivo in non-human primates.^[4][12][3] In addition, whereas MDMA and (S)-MDMA are well-balanced SNDRAs, (R)-MDMA is comparatively much less potent as a dopamine releasing agent (~11-fold less potent in releasing dopamine than serotonin), and could be thought of instead more as a serotonin–norepinephrine releasing agent (SNRA) than as an SNDRA.^{[4][12][3][5]} In non-human primates, (S)-MDMA demonstrated significant dopamine transporter (DAT) occupancy, whereas DAT occupancy with (R)-MDMA was undetectable.^[3] Similarly, MDMA and (S)-MDMA were found to increase dopamine levels in the striatum in rodents and non-human primates, whereas (R)-MDMA did not increase striatal dopamine levels.^[3][20] As such, (R)-MDMA may be less psychostimulant-like than MDMA or (S)-MDMA.^[2][5]

In addition to its actions as an SNDRA, MDMA has weak affinity for the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors, where it acts as an agonist.^[3] (R)-MDMA shows higher affinity for the serotonin 5-HT_2A receptor than (S)-MDMA or MDMA.^[3] In addition, (R)-MDMA is more potent as an agonist of the serotonin 5-HT_2A receptor, acting as a weak partial agonist of this receptor, whereas (S)-MDMA shows very little effect.^[3] Conversely however, (S)-MDMA is more potent as an agonist of the serotonin 5-HT_2C receptor.^[3][21] Based on these findings, it has been hypothesized that (R)-MDMA may be more psychedelic-like than (S)-MDMA.^[2] However, although (R)-MDMA partially substitutes for lysergic acid diethylamide (LSD) in animal drug discrimination tests, it did not produce the head-twitch response, a behavioral proxy of psychedelic effects, at any tested dose.^[22] In any case, findings in this area are conflicting.^[23] (R)-MDMA is inactive as an agonist of the human TAAR1, whereas (S)-MDMA shows very weak potency as an agonist of the receptor (EC₅₀Tooltip half-maximal effective concentration = 74,000 nM).^[24]

MDMA is a well-known serotonergic neurotoxin and this has been demonstrated both in animals and in humans.^[3] There is evidence that the serotonergic neurotoxicity of MDMA may be driven primarily by (S)-MDMA rather than (R)-MDMA.^[3] (R)-MDMA shows substantially lower or potentially no neurotoxicity compared to (S)-MDMA in animal studies.^[3] This has been the case even when doses of (R)-MDMA were increased to account for its lower potency than (S)-MDMA.^[3] However, more research is needed to confirm this in other species, such as non-human primates.^[3] In contrast to (S)-MDMA, (R)-MDMA does not produce hyperthermia in rodents, and this may be involved in its reduced risk of neurotoxicity, as hyperthermia augments and is essential for the serotonergic neurotoxicity of MDMA.^[3][5] The reduced potency of (R)-MDMA as a dopamine releasing agent may also be involved in its reduced neurotoxic potential, as dopamine release is likewise essential for the neurotoxicity of MDMA.^[3] The hyperthermia of MDMA may in fact be mediated by dopamine release.^[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]

(R)-MDMA and (S)-MDMA have shown equivalent effects in terms of inducing prosocial behavior in monkeys.^[3] However, (S)-MDMA shows higher potency, whereas (R)-MDMA shows greater maximal effects.^[3] Conversely, (S)-MDMA does not increase prosocial behavior in mice, whereas both MDMA and (R)-MDMA do so.^[3][5] MDMA and (S)-MDMA increase locomotor activity, a measure of psychostimulant-like effect, in rodents, whereas (R)-MDMA does not do so.^[5] (R)-MDMA likewise showed fewer reinforcing effects than (S)-MDMA in non-human primates.^[3] These findings further add to (R)-MDMA showing reduced psychostimulant-like and addictive effects compared to MDMA and (S)-MDMA.^[3]

MDMA, MDA, and enantiomers at serotonin 5-HT₂ receptors

Compound	5-HT2A		5-HT2B		5-HT2C
	EC50 (nM)	Emax	EC50 (nM)	Emax	EC50 (nM)	Emax
Serotonin	53	92%	1.0	100%	22	91%
MDA	1,700	57%	190	80%	ND	ND
(S)-MDA	18,200	89%	100	81%	7,400	73%
(R)-MDA	5,600	95%	150	76%	7,400	76%
MDMA	6,100	55%	2,000–>20,000	32%	ND	ND
(S)-MDMA	10,300	9%	6,000	38%	2,600	53%
(R)-MDMA	3,100	21%	900	27%	5,400	27%
Notes: The smaller the Kact or EC50 value, the more strongly the compound produces the effect. Refs: [25][12][26]

The elimination half-life of (S)-MDMA is 4.1 hours, whereas the half-life of (R)-MDMA is 12 to 14 hours.^[1][2] In the case of racemic MDMA administration, the half-life of (S)-MDMA is 5.1 hours and the half-life of (R)-MDMA is 11 hours.^[2] (R)-MDMA shows cytochrome P450 CYP2D6 inhibition and lower levels of the metabolite 4-hydroxy-3-methoxymethamphetamine (HMMA) than (S)-MDMA.^[2]

(R)-MDMA was first described in the scientific literature in enantiopure form by 1978.^[6] It was described in a paper authored by Alexander Shulgin, David E. Nichols, and other colleagues.^[6]

As an enantiomer of MDMA, (R)-MDMA is a Schedule I controlled substance in Canada.^[27]

As an enantiomer of MDMA, (R)-MDMA is a Schedule I controlled substance in the United States.^[27]

(R)-MDMA is under development separately by Empath Biosciences (EmpathBio) and MindMed.^{[9][11][10][28]} It is being developed by Empath Biosciences for the treatment of PTSD and social phobia^[9][11] and it is being developed by MindMed for the treatment of PDDs or autism.^[10][28] As of February 2026, the drug is in phase 2 clinical trials for social phobia and autistic spectrum disorders, whereas no recent development has been reported for PTSD.^[9][10] The results of a phase 2a trial for treatment of social phobia have been released, with the drug showing moderate effectiveness and a generally favorable safety profile for this indication.^[29]