Effects of the Psychedelic Amphetamine MDA (3,4-Methylenedioxyamphetamine) in Healthy Volunteers

The drug MDA, an entactogen similar to MDMA (ecstasy), produces longer-lasting emotional and physiological effects than MDMA. In a controlled experiment with healthy volunteers, a single oral dose of 1.4 mg/kg MDA increased heart rate, blood pressure, and stress hormones (cortisol and prolactin) to levels comparable to those from a 1.5 mg/kg dose of MDMA. However, participants' self-reported drug effects from MDA remained elevated for at least 8 hours, whereas MDMA effects subsided by 6 hours. Blood measurements showed that MDA and its metabolite HMA reached peak concentrations of about 229 µg/L and 92 µg/L, respectively. Because the two drugs had similar blood-level profiles, the longer duration of MDA's effects likely stems from differences in how it acts on the brain rather than from slower elimination.

Study at a glance

Abstract

Entactogens such as 3,4-Methylenedioxymethamphetamine (MDMA, "molly", "ecstasy") appear to have unusual, potentially therapeutic, emotional effects. Understanding their mechanisms can benefit from clinical experiments with related drugs. Yet the first known drug with such properties, 3,4-Methylenedioxyamphetamine (MDA), remains poorly studied and its pharmacokinetics in humans are unknown. We conducted a within-subjects, double-blind, placebo-controlled study of 1.4 mg/kg oral racemic MDA and compared results to those from our prior similar studies with 1.5 mg/kg oral racemic MDMA. MDA was well-tolerated by participants. MDA induced robust increases in heart rate and blood pressure and increased cortisol and prolactin to a similar degree as MDMA. MDA self-report effects shared features with MDMA as well as with classical psychedelics. MDA self-report effects lasted longer than those of MDMA, with MDA effects remaining elevated at 8 h while MDMA effects resolved by 6 h. Cmax and AUC0-∞ for MDA were 229 ± 39 (mean ± SD) and 3636 ± 958 µg/L for MDA and 92 ± 61 and 1544 ± 741 µg/L for the metabolite 4-hydroxy-3-methoxyamphetamine (HMA). There was considerable between-subject variation in MDA/HMA ratios. The similarity of MDA and MDMA pharmacokinetics suggests that the greater duration of MDA effects is due to pharmacodynamics rather than pharmacokinetics.